- Email: [email protected]
Research and Application of Glycoprotein Sensors Based on Glycosyl Recognition
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY Volume 47, Issue 9, September 2019 Online English edition of the Chinese language journal
Cite this article as: Chinese J. Anal. Chem., 2019, 47(9): 1283–1292
REVIEW
Research and Application of Glycoprotein Sensors Based on Glycosyl Recognition LIANG Jun-Yu, TONG Pei-Hong, LI Jian-Ping* College of Chemical and Bioengineering, Guilin University of Technology, Guangxi Key Laboratory of Electrochemical and Magnetochemical Function Materials, Guilin 541004, China
Abstract:
Glycoprotein is a binding protein whose structure is mainly determined by the content of sugars and proteins and the
peptide bonds to which it binds. There are many kinds of glycoproteins, and they can be classified into lectin, hormone, enzyme and immunoglobulin according to the clinical role in the medical field. Glycoproteins have a variety of biological functions and are of great significance in the medical and biological fields. In order to study the biological information related to glycoproteins, it is necessary to establish a highly sensitive and efficient analytical detection method for glycoproteins. The assay of glycoproteins includes separation and purification method, structural analysis and content determination. The commonly used methods for glycoproteins determination are mass spectrometry (MS), chromatography-mass spectrometry, surface excimer resonance, and enzyme-linked immunosorbent assay (ELISA), etc. In recent years, in the detection of glycoproteins, the research and application of sensors have gradually increased. This paper briefly summarized the analysis methods of glycoproteins and reviewed the research and application of glycoprotein biosensors based on glycosyl recognition. The glycoprotein biosensors including electrochemical sensors, optical sensors and mass sensors were introduced in detail. The future development direction of glycoprotein sensors was also prospected. Key Words:
Glycoprotein; Glycosyl; Sensors; Review
1 Introduction With the development of society and economy, the environment issues are becoming more and more serious, and human health is facing many threatens. Most diseases are caused by the lesion of human cells, such as tumors and cancer. Therefore, the timely and accurate diagnosis of diseases in early stage is of great significance for targeted clinical treatment and later rehabilitation[1]. In the process of cell changes, normal cells become uncontrolled malignant proliferating cells due to the action of carcinogenic factors, producing substances such as glycoproteins on the surface of cancer cells. Glycoproteins are closely related to the occurrence of various diseases and have been used as clinical biomarkers and therapeutic targets. Therefore, the analysis and
detection of glycoproteins is very important, and the development of rapid and accurate methods for the detection of glycoproteins has been widely concerned by researchers[2,3]. Glycoprotein is a kind of combinational protein, in which the composition of sugar contains a lot of structural information and can be used as the main specific recognition site. In the detection of glycoproteins, the characteristic glycosyl can be used for specific identification with lectins, antibodies or other molecules with glycosyl affinity. Glycoprotein biosensors have many advantages including high sensitivity, good selectivity and ease to use. This paper reviewed the research progress of glycoprotein analysis and glycoprotein biosensors based on glycosyl recognition.
2 Glycoprotein
________________________ Received 8 May 2019; accepted 18 June 2019 *Corresponding author. E-mail: [email protected] This work was supported by the National Natural Science Foundation of China (No. 21765006) and the Natural Science Foundation of Guangxi, China (No. 2015GXNSFFA139005). Copyright © 2019, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Published by Elsevier Limited. All rights reserved. DOI: 10.1016/S1872-2040(19)61185-0
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
Glycoproteins are widely presented in plants and animals, which are carriers of cell information. Glycoproteins are complex sugars composed of branched oligosaccharide chains covalently linked with polypeptide chains. Glycoproteins are widely distributed in nature, including 60 or 70 kinds of studied plasma proteins, some enzymes, hormones, and lectins isolated from plants or animals. Many early researches on sugar-protein interactions focused on identification of sugars by enzymes, such as endoglycosidase lysozyme which broke down cell walls of bacteria, and enzymes involved in intermediate metabolism. Fleming, Chain and Corey won the Nobel Prize in 1945 for discovering the antibacterial effects of lysozyme and penicillin. In the late 1960s, Phillips et al[4] obtained the three-dimensional structure of lysozyme from the complex formed by lysozyme and tetrasaccharide. In addition, other historic studies on the three-dimensional structure of glycoproteins are ConA (crystal structure of ConA was reported in 1972[5]) and hemagglutinin of influenza virus (crystal structure of ConA was reported in 1981 [6]). 2.1
Classification of glycoprotein
There are many kinds of glycoproteins. According to the type of peptide bond, they can be divided into o-connexin and n-connexin[7]. According to the differences in sugar and protein content in glycoproteins, they can be divided into proteoglycan[8] and glycoprotein[9]. The main difference between the two is that proteoglycan is mainly composed of glycan and assisted by protein, and the sugar content can reach 98%. Glycoproteins can be classified into soluble glycoproteins, membrane-bound glycoproteins and structural glycoproteins based on their existing state. Soluble glycoproteins include enzymes (e.g., nucleases, proteases, glycosidases), peptide hormones (e.g., chorionic gonadotropin, luteinizing hormone, thyrotropin, erythropoietin), antibodies, complement, and certain growth factors, interferons, statins, lectins and toxins. Membrane-bound glycoproteins include enzymes, receptors, lectins and carrier proteins. Structural glycoproteins include collagen and various non-collagen Table 1 Classification
Name
glycoproteins (fibronectin, laminin, etc.). There are many kinds of glycoproteins which exist widely in the body of organisms and are closely related to the growth of life. They have important research significance and clinical functions in the medical field, as shown in Table 1. 2.2
Clinical role of glycoproteins
Glycoprotein has important clinical significance. Glycoproteins include many indicators of clinical diagnosis or disease monitoring, which can not only provide information for clinical diagnosis, but also facilitate the judgment of recovery and interventional treatment. Glycoprotein-related diseases are represented by tumors, cancers and other diseases that cause great damage to the body. Zhou et al [22] established a enrichment strategy of glycoprotein based on sugar and lectin affinity, which was used in glycoprotein fucus glycosylation mass spectrum analysis. The results showed that the protein fucus glycosylation analysis helped to further understand the occurrence and development of prostate cancer, and provide effective reference basis for clinical judgment of invasion. In addition, glycoprotein also can be applied to the clinical diagnosis of pregnancy. For instance, high glycosylation human chorionic gonadotropin (hCG) is a related molecule of fluff gonadotropin hCG, which is secreted by undifferentiated or poorly differentiated cells of trophoblast cells. The rules of hCG protein skeleton structure is basically the same; the difference is that the modified sugar base ratio increased significantly in the process of expression of high glycosylation hCG, and the modified sugar-based molecular mass is bigger, with more complicated structure. High glycosylated hCG level is closely related to the development of early pregnancy and the occurrence and development of trophoblastic disease. Similar studies have been carried out in clinical diagnosis of animal pregnancy. de Rensis et al[23] improved the pregnancy rate of cows by using equine chorionic gonadotropin (eCG) for treatment and control of reproductive activities. Glycoproteins can also be used in clinical interventional therapy. Zhang et al[24] isolated and characterized a novel
Classification and role of glycoprotein Effect
Reference
Lectin
Animal lectin Plant lectin
Identification and adhesion of cells and molecules, such as tumor metastasis, etc.
[10] [11]
Hormone
Chorionic gonadotropin (CG) Follicle stimulating hormone (FSH) Luteinizing hormone (LH) Thyroid stimulating hormone (TSH)
It acts on specific tissues and organs, binds to the corresponding protein-coupled receptors, activates the secondary messenger pathway, promotes the release of glands, and plays an important regulatory role in growth and development.
[12] [13] [14] [15]
Enzyme
Lipoprotein lipase Tissue plasminogen activator Hyaluronidase Hepatic lipase
Participation in the body's metabolic system, it has the ability to improve the permeability of tissue fluid, enzyme activity as an indicator of clinical diseases such as leukemia, prostate tumors.
[16] [17] [18] [19]
Immunoglobulin
IgG/IgM/IgA/IgD/IgE
Complement activation, receptor binding, molecular recognition, molecular polymerization, etc.
[20] [21]
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
lectin with anti-tumor activity from red mushroom for the first time, which provided an effective idea for clinical treatment of tumor. In addition, one of the potential mechanisms of MDR is that the over-expression of p-glycoprotein (p-gp) in multidrug resistant cells increases the efflux of anticancer drugs. Li et al[25] ynthesized a soluble, water-soluble, single-walled carbon nanotube (anti-p-gp) antibody using MDR of p562 human leukemia cells, effectively overcoming multidrug resistance of human leukemia cells. Therefore, it is necessary to develop a simple and efficient method for glycoprotein detection.
3 Methods for glycoprotein analysis Glycoprotein analysis includes glycoprotein separation, structure analysis and identification, and content determination. Glycoprotein analysis is mainly based on the molecular size, shape, polarity, charge-to-mass ratio and intermolecular interaction. Single component glycoproteins are usually isolated from crude glycoproteins prior to glycoprotein analysis. 3.1
Separation and purification methods
The isolation and purification of glycoproteins, refers to the process of removing impurities from the crude glycoprotein products to obtain a single glycoprotein [26] is the basis of structural identification. Because lectin can recognize and bind to specific monosaccharide or sugar chain structure, immobilized lectin affinity chromatography[27] is the most commonly used method for isolation and purification of glycoproteins. Chromatographic separation technology usually mixes several methods to separate glycoproteins based on different molecular shapes and sizes and different charges of proteins in solutions with different pH values, including high performance liquid chromatography (HPLC), ion exchange chromatography, gel column chromatography and affinity chromatography. Electrophoretic separation is performed based on the characteristics of different charge loads of glycoproteins and different mobility under electric field [28]. Membrane separation is mainly a rough classification of glycoproteins with different molecular weights, which requires further separation by chromatography or electrophoresis. However, fractional precipitation method uses the differences in the size and solubility of glycoprotein molecules to achieve separation[29]. Borate affinity material (BAMs) has a unique affinity effect on cis-diol biomolecules, which can be used for selective separation and enrichment of sugars, glycosyl and glycoproteins. In recent years, it has also received more and more attention[30]. In the past, three major bottlenecks including non-biocompatible binding pH, weak affinity and selective operation difficulty existed in the practical application of BAMs. However, a variety of new
BAMs have emerged in recent years, which make the application prospect of BAMs broader[31]. Liu et al[32] proposed a variety of strategies, including the boron affinity lithography imprinting method based on boric acid affinity and highly specific molecular imprinting technology, and the boron affinity controllable directional imprinting method, which solved the above problems well and effectively improved the affinity and selectivity of BAMs. 3.2
Structural analysis methods
At present, the structural analysis methods of glycoproteins include methylation analysis[33], iodine oxidation[34], nuclear magnetic resonance (NMR)[35], chromatography-MS[36], x-diffraction[37], etc., mainly involving molecular weight, polysaccharide and protein content, amino acid composition and sequence, sugar chain structure and other molecular information[38]. The information of sugar chain structure is essential in the analysis of glycoprotein structure, including monosaccharide composition, connection mode and branch structure. Generally, such information is obtained through release of sugar chain. Currently, the release of n-sugar chain adopts the enzymatic hydrolysis method [39], such as endoglycosidase, trypsin, etc. O-sugar chain is released by chemical method, such as beta-elimination method[40]. The primary structure of polysaccharides can be identified by HPLC, NMR and MS. High-resolution NMR technology can study the three-dimensional structure of sugar chains, and express structural characteristics through chemical displacement, integral area, coupling constant and other information[41]. The MS method is mainly used for the analysis of sugar chain structure, including electrospray ionization MS (ESI-MS), matrix-assisted laser-desorption time-of-flight MS (MALDI-TOF-MS) and fast atom bombardment MS, etc., which can be used for the analysis of connection mode of sugar peptide bonds and glycosylation sites. 3.3
Methods for determination of sugar and protein content
The determination of polysaccharide content is usually based on the reducibility of sugar, such as phenol-sulfuric acid method[42]. In the determination of protein content, proteins are usually combined with dyes to form compounds, and the content is determined according to the color depth, such as the forinol method[43]. The molecular weight and isoelectric point of glycoprotein samples can be quickly identified by gel filtration chromatography or polyacrylamide gel electrophoresis. Secondly, the structural information of amino acids in proteins can be determined by ion exchange chromatography, HPLC and capillary electrophoresis. In addition, the specificity of characteristic glycosyl or
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
sugar chain in glycoproteins is the focus of analysis and detection. The common detection method of glycoproteins is MS method[44], and the combination method of LC and MS has attracted more and more attention[45]. However, these methods have some disadvantages, such as high cost of instrument, requirement of professional skills of operators and complex pretreatment of samples. Therefore, it is of great significance to develop a mild and efficient method for the isolation and detection of glycoproteins. Chip method solves these issues very well. Instead of releasing the sugar chain from the glycoprotein, chip method can directly detect the sugar chain of the glycoprotein[46]. Chip methods include surface exciton resonance, enzyme-linked immunosorbent assay[47] and biosensors[48]. The detection principle of this method is to fix monosaccharide, lectin[49] and antibody on the matrix, which specifically bind to glycoproteins to generate detection signals. Biosensors are the most widely used biosensors, and the combination of sensor technology to prepare glycoprotein biosensors can quickly, effectively and sensitively detect glycoprotein molecules qualitatively and quantitatively[50].
4
Classification and application of glycoprotein sensors for glycosyl recognition
Biosensors are a very active research field at present, the focus of which is to develop bioactive materials that can be used as sensitive elements, such as biological macromolecules[51]. Since the 1980s, researches on biosensors including glycoprotein biosensors have attracted more and more attention, and glycoprotein biosensors using antibodies, hormones, receptors, molecularly imprinted membranes and other recognition elements have been developed. At present, biosensors are in the early stage of detecting glycan and lectin. So far, the most commonly used method in carbohydrate biosensors is to detect carbohydrate compounds based on a series of lectin/carbohydrate identification on lectin array[52]. Lectin arrays have been used effectively to analyze glycoproteins as well as proteoglycans on the surface of bacterial and mammalian cells. The characteristic glycosyl or sugar chain of glycoproteins is the key to the selective recognition of glycoproteins by sensors. In addition, the Table 2 Glycoprotein target Carcinoembryonic antigen(CEA)
glycoprotein sensors with high sensitivity and low detection limit can be developed by combining catalytic effect or doping nanomaterials and other sensitization methods[53]. There are many kinds of sensors based on glycosyl-based glycoprotein recognition. According to the signal conversion type, sensors can be divided into electrochemical type, optical type and mass type. 4.1
Electrochemical sensors
The sugar moiety recognition-based electrochemical sensors of glycoproteins which combines the high sensitivity of electrochemical detection method and the inherent biological selectivity of glycoprotein molecules can selectively identify the targets by specific recognition of the glycogroup or sugar chain of glycoproteins based on the generating electrical signals, so as to realize qualitative or quantitative detection. Currently, electrochemical sensors are widely used as a kind of glycoprotein biosensors [54,55], which can be divided into current type, impedance type and potential type[56]. Most of them are current type and impedance type. Some researches on glycoprotein sensors based on lectin specific recognition of sugar groups are listed in Table 2. Among them, the current mode is through modification with lectin or carbohydrate recognition elements such as molecularly imprinted membrane electrode, and the electroactive probe electron will transfer on the electrode surface when the glycoprotein molecules are specifically bound on the electrode surface. With adsorption of different concentrations of target glycoprotein molecule, the electron transfer rate changes on the surface of the electrode, resulting in the changes in current[57]. The carbohydrate recognitionbased glycoprotein impedance type sensors is to use lectins and specific binding of sugar-based sugar chain, in the process of detection, because the heavy adsorption moleculars hinder the electron transfer of electroactive probe on the sensor surface, the impedance value of the sensors shows a certain linear relationship with glycoprotein concentration, so as to realize the quantitative and qualitative test of glycoprotein[58,59]. The detection sensitivity of EIS sensors can be improved by adding sensitizing material. Common sensitizers include
List of glycoprotein electrochemical sensors based on lectin-specific glycosylation Output signal Current
Lectin
Detection range –1
Limit of detection –1
Reference
Concanavalin A (ConA)
1–10 ng mL
0.03 ng mL
[60]
Wheat germ agglutinin (WGA)
1–100 ng mL–1
0.1 ng mL–1
[61]
Sambucus nigra lection (SNA)
100 μg/mL
100 ag mL–1
[62]
0.68 g mL–1
[63]
> 1 g mL–1
1 pg mL–1
[64]
1–1105 ng mL–1
1 ng mL–1
[65]
Electrochemical Alpha fetoprotein (AFP)
Impedance Spectroscopy (EIS)
Prostate specific antigen (PSA)
EIS
Fetuin (FET)
EIS
Vicia villosa lectin (VVA)
Fetuin (FET)
EIS
Peanut agglutinin (PNA)
Antigens (ProBL)
Current
WGA
–1
> 2.25 g mL
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
AuNPs with high conductivity and biocompatibility, graphene and carbon nanotubes with high electron transfer rate, and metal-organic frame materials with high specific surface area and frame stability. Klukova et al[66] prepared an impedance sugar-based recognition sensors based on the specific recognition of ConA toward mannose. To further improve the sensitivity of the sensors, they took advantage of the high conductivity of graphene oxide (GO) modified on the surface of the electrode to increase the electron transfer rate. In addition, some lectins have strong affinity to glycosyl groups. Bertok et al[67] prepared a ultrasensitive label-free agglutinin EIS biosensor based on strong specificity of SNA I toward glycoprotein-fetoglobulin containing sialic acid sugar group. The detection range covered 7 orders of magnitude, and the detection limit was lower than 0.54 fM (Fig.1). Hu et al[68] developed a new type of EIS sensor by modifying ConA that could specially identify mannose on the gold electrode on the basis of the interaction of carbohydrates and lectin. This sensor could be used to directly identify mannose glycoprotein on the surface of the cancer cells or sugar peptide, and was successfully applied to the detection of liver cancer cells (Fig.2). Molecular imprinting technology[69] has the characteristics of structure-activity reservation, environmental tolerance and high selectivity, and is a good development direction to apply
Fig.1
Fig.2
molecular imprinting technology to the detection of glycoproteins. In the past few years, the imprinting of biological macromolecules has been very challenging, especially for proteins. This is because the large size of proteins makes it difficult to remove them from highly crosslinked polymer networks, leading to great obstacles in the research and application of glycoprotein imprinting sensors. Liu et al[70] proposed an imprinting strategy that combined the affinity of borate with the advantages of molecular imprinting sensors, namely, photolithography of borate affinity molecular imprinting. In this work, the glycoprotein template and monomer formed covalent compounds by borate affinity function, and the boric acid complex was polymerized with crosslinking agent under UVlight irradiation. By simply adjusting solution pH value, the imprinted cavity was obtained. This strategy had good biological compatibility in a wide pH range, strong affinity, high specificity and good anti-jamming capability. However, this method had some limitations. For example, it required that the substrate must be able to accept ultraviolet radiation to generate polymerization. Therefore, the team further developed another simple and more universal method, namely, controllable directional surface imprinting based on the affinity of borates[71]. In addition, inspired by the antigendetermining imprinting method and combined with the
Schematic of an ultrasensitive label-free lectin impedance biosensors[67]
Schematic diagram of EIS biosensor based on interaction of carbohydrates and lectins [68]
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
glycation alteration behavior of the tumor[72], our research group[73] proposed a new macromolecular imprinting strategy based on glycation, which used the characteristic glycosyl of tumor markers as the imprinting template to recognize the whole glycoprotein macromolecule. As shown in Fig.3, the polysaccharide molecularly imprinted sensors were successfully prepared with the sugar-based slea structure featured by excessive expression at the end of the sugar antigen CA19-9 as template molecule and o-phenylendiamine as functional monomer. By using potassium ferricyanide as ion probe, the prepared sensors were applied to the quantitative detection of CA19-9 in concentration range of 0.1–5 U mL–1 by indirect method, with a detection limit of 0.028 U mL–1. The prepared imprinting sensors also effectively solved the difficulty of large molecular imprinting of glycoproteins. Compared with traditional immunoassay, the sensors had many advantages including low cost, simple and rapid preparation. This study provided a non-immunoassay
Fig.3
Fig.4
method for the detection of glycoproteins with high sensitivity, selectivity, convenience, efficiency and applicability. 4.2
Optical sensors
The optical sensors that can detect glycoproteins by identifying glycosyl groups are usually based on surface plasmon resonance (SPR) [74], fluorescence [75] and other principles to directly or indirectly obtain the changes of optical signals, thus achieving the detection of analyte. The SPR sensors do not need to be labeled, and the biospecific interaction occurs directly on the surface of the sensors chip. Based on SPR technology and specific affinity of ConA and SNA on mannose and fucose, Geuijen et al[76] built a multiple SPR imaging platform for specificity recognition of sugar-based glycoprotein characteristics of lectin, which provided an important reference (Fig.4) for unmarked immunoassay of glycoprotein. In addition, Angeloni et al[77]
Construction of CA19-9 electrochemical sensor based on glycosylation change[73]
Construction of label-free detection of lectin-glycosyl sensors based on surface plasmon resonance[76]
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
made use of the specific recognition effect of lectin and sugar chain components to modify lectin on the surface of glass slides. Based on this, they prepared fluorescence sensors through fluorescence labeling and other detection methods for the efficient analysis of sugar chain structure of glycoproteins on the surface of living cells. In recent years, based on the covalent bonding between boric acid and sugar, high specificity of molecularly imprinted polymers and surface enhanced Raman scattering technique, etc., Liu et al put forward two new optical sensing methods, boron affinity sandwich method (BASA)[78] and plasma immune sandwich method (PISA)[79–81], for determination of trace amounts of glycoprotein in complex samples. The prepared sensors had rapid detection speed and high sensitivity, showing broad application prospects. Fluorescent probes play an indispensable role in the study of optical sensors for detection of glycoproteins. Because fluorescent probe binds with antigens and antibodies and does not affect their activity, it is usually used for labeling antigens and antibodies in glycoprotein fluorescence immunoassay[82]. However, it is generally difficult to obtain specific antibodies and the cost is high. Jiang et al[83] synthesized two new sugar-based fluorescent probes, PT-Man and PT-Gal, based on the interaction between sugar and lectin, and further improved the sensitivity of the sensors by using GO as a sugar base platform (the detection limit reached 10‒9 M, Fig.5). This method provided a reference basis for the study of the acceptor reaction between cell, known or unknown. 4.3
Quality sensors
The quality sensors include quartz crystal microbalances (QCM) sensors[84] and surface acoustic wave sensors[85], etc. In general, the changes of parameters of the surface of the
Fig.5
sensors material, such as piezoelectric or pressure, can directly result in the quality signal change, which can be converted to electrical signals or directly calculate quality signal changes value. Therefore, the quantitative analysis can be performed according to the linear relationship of the change of quality signal value and the analyte concentration. At present, the carbohydrate recognition-based sensors[86,87], which are mainly combined with QCM design for analysis, are prepared by fixing the sugar-based lectin with specific recognition on the surface of the functionalized sensors platform. Because the quality signal of sensing platform changes with the change of resonance frequency in a certain proportion, the quantitative detection of glycoprotein can be achieved. Based on epitope imprinting technology, Lu et al[88] developed a new type of sensor by polymerization of imprinted film on the surface of QCM with dopamine as the functional monomer and HIV-1 glycoprotein fragments of synthetic peptide as template molecule. This sensor not only had a strong affinity for template peptide, but also could specifically detect HIV surface glycoprotein GP41, with a detection limit of 2 ng mL–1 (Fig.6). Compared with the conventional enzyme-linked immunoassay, the sensor had a better practical analysis performance. In addition, it could also be used for sensitive detection of cells[89] and antigens[90].
5
Conclusions and prospects
Glycoproteins have complex biological structural information and can directly or indirectly participate in biomolecular recognition. Compared with the traditional MS method, the glycoprotein sensors with high specificity and high sensitivity constructed by using glycosimprinting and boric acid affinity imprinting have the characteristics of rapid detection and high sensitivity, which is an ideal development direction for
Schematic diagram of fluorescent sensor constructed by novel glycosyl fluorescent probe [83]
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
Fig.6
Schematic diagram of detection of HIV-associated glycoprotein by surface-imprinted quartz crystal microbalance[88]
glycoprotein research. Borate affinity molecular imprinting membrane or glycolic imprinting membrane was used to construct glycoprotein sensors with high specificity, convenience and efficiency. On the other hand, it makes up for the shortage of template molecules that are difficult to elute in the study of glycoprotein imprinting in the past. In addition, the specific binding of lectin and glycosyl can be used to further expand the research field of glycosyl sensors. At present, glycoprotein biosensors are in the rapid development stage, and some researchers have achieved commercial promotion and application, such as pregnancy test stick, providing reliable reference for early detection and timely treatment of related diseases in the detection and analysis of tumor markers. With the development of life analytical science, glycoprotein biosensors based on glycosylation recognition still have great space for improvement. They can be applied to the research of cells, viruses and even individuals with vital signs by combining new nanomaterials and imaging technologies, which will be the research direction in the future.
Chinese J. Chromatogr., 2018, 36(12): 1197–1205 [4]
Phillips D C. Sci. Am., 1966, 215(5): 78–93
[5]
Hardman K D, Ainsworth C F. Biochemistry, 1972, 11(26): 4910–4919
[6]
Wilson I A, Skehel J J, Wiley D C. Nature, 1981, 289(5796):
[7]
Jensen P H, Karlsson N G, Kolarich D, Packer N H. Nat.
366–373 Protoc., 2012, 7(7): 1299–1310 [8]
Merkle R K, Poppe I. Methods Enzymol., 1994, 230(4): 1–15
[9]
Alexander S P, Benson H E, Faccenda E, Pawson A J, Sharman J L, Speding M, Peter J A, Harmar A J. Brit. J. Pharmacol., 2014, 170(8): 1459–1581
[10] Stern D, Pauly D, Zydek M, Müller C, Avondet M A, Worbs S, Lisdat F, Dorner M B, Dorner B G. Biosens. Bioelectron., 2015, 78: 111–117 [11] Toshima T, Shirabe K, Ikegami T, Yoshizumi T, Kuno A, Togayachi A, Gotoh M, Narimatsu H, Korenaga M, Mizokami M. J. Gastroenterol., 2015, 50(1): 76‒84 [12] Diana T, Krause J, Olivo P D, König J, Kanitz M, Decallonne B, Kahaly G J. Clin. Exp. Immunol., 2017, 189(3): 304–309 [13] Pocius K D, Maurer R, Fortin J, Goldberg A B, Bartz D.
References
Contraception, 2015, 91(6): 503–506 [14] Santi D, Casarini L, Alviggi C, Simoni M. Front. Endocrinol.,
[1]
Kreicbergs U, Valdimarsdóttir U, Steineck G, Henter J I. Lancet, 2004, 364(9436): 787–789
[2]
Beck W T, Grogan T M, Willman C L, Cordoncardo C, Parham D M, Kuttesch J F, Andreeff M, Bates S E, Berard C W, Boyett
2017, 8: 114 [15] Vestergaard E T, Schjørring M E, Kamperis K, Petersen K K, Rittig S, Juul A, Kritstensen K, Birkebæk N H. Eur. J. Endocrinol., 2017, 176(6): 747–753
J M, Brophy N A, Broxterman H J, Chan H S, Dalton W S,
[16] Calderon R M, Diaz S, Szeto A, Llinas J A, Hughes T A,
Dietel M, Fojo A T, Gascoyne R D, Head D, Houghton P J,
Mendez A J, Goldberg R B. J. Clin. Endocr. Metab., 2015,
Srivastava D K, Lehnert M, Leith C P, Paietta E, Pavelic Z P, Weinstein R. Cancer Res., 1996, 56(13): 3010–3020 [3] Zhao Y, Zhang Y, Wang M C, Meng B, Ying W T, Qian X H.
100(7): 2581–2588 [17] Gong H, Chao Y, Xiang J, Han X, Song G, Feng L, Liu J, Yang G, Chen Q, Liu Z. Nano Lett., 2016, 16(4): 2512‒2521
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
[18] Moore H B, Moore E E, Gonzalez E, Hansen K C, Dzieciatkowska M, Chapman M P, Sauaia A, West B, Banerjee A, Silliman C C. Shock, 2015, 43(1): 39–46 [19] Reiner Ž, Guardamagna O, Nair D, Soran H, Hovingh K, Bertolini S, Jones S, Ćorić M, Calandra S, Hamilton J, Eagleton T, Ros E. Atherosclerosis, 2014, 235(1): 21–30 [20] Liang L, Willis-Owen S A, Laprise C, Wong K C, Davies G A, Hudson T J, Binia A, Hopkin J M, Yang I V, Grundberg E, Busche S, Hudson M, Rnnblom L, Pastinen T, Schwartz D A, Lathrop G M, Moffatt M F, Cookson W O. Nature, 2015, 520(7549): 670–674 [21] Walker B A, Wardell C P, Brioli A, Boyle E, Kaiser M F, Begum D B, Dahir N B, Johnson D C, Ross F M, Davies F E. Blood Cancer J., 2014, 4(3): e191 [22] Zhou J, Yang W, Hu Y, Höti N, Liu Y, Shah P, Sun S, Clark D, Thomas S, Zhang H. Anal. Chem., 2017, 89(14): 7623–7630 [23] de Rensis F, López-Gatius F. Reprod Dom. Anim., 2014, 49(2): 177–182 [24] Zhang G, Sun J, Wang H, Ng T B. Phytomedicine, 2010, 17(10): 775–781 [25] Li R, Wu R, Zhao L, Wu M, Yang L, Zou H. ACS Nano, 2010, 4(3): 1399–1408 [26] Ugozzoli M, Chiu A. Biotechniques, 1992, 12(2):187–190 [27] Meiniger M, Stepath M, Henning R, Cajic S, Rapp E, Rotering H, Wolff M W, Reichl U. J. Chromatogr. B, 2016, 1012-1013: 193–203 [28] Cong W, Zhou A, Liu Z, Shen J, Zhou X, Ye W, Zhu Z, Zhu X, Lin J, Jin L. Anal. Chem., 2015, 87(3): 1462–1465 [29] Arnold L, Chen R. Biotechnol. Bioeng., 2014, 111(2): 413–417 [30] Nishiyabu R, Kubo Y, James T D, Fossey J S. Chem. Commun., 2011, 47(4): 1106–1123 [31] Li D J, Chen Y, Liu Z. Chem. Soc. Rev., 2015, 44(22): 8097–8123 [32] Liu Z, He H. Accounts Chem. Res., 2017, 50(9): 2185–2193 [33] Shajahan A, Supekar N T, Heiss C, Ishihara M, Azadi P. Anal. Chem., 2017, 89(20): 10734–10743 [34] Giannini G, Alekseeva A, Naggi A, Salvini L, Tei L, de Santis R. Anal. Bioanal. Chem., 2018, 410(2): 553–564 [35] Gallo M, Matteucci S, Alaimo N, Pitti E, Orsale M V, Summa V, Cicero D O, Monteaqudo E. J. Pharm. Anal., 2019, 167: 21–29 [36] Huang Y L, Jhou B Y, Chen S F, Khoo K H. Anal. Sci., 2018, 34(9): 1049–1054 [37] Kent S B H. Protein Sci., 2019, 28(2): 313–328 [38] HofbauerováK, Jr K V, Sýkora J, Karpenko V. Biophys. Chem., 2003, 103(1): 25–33 [39] Yan J P, Liu Y R, Wang K X, Li D Y, Hu Q Q, Zhang W J. Plant Sci., 2018, 276: 143–151 [40] Eckmair B, Jin C S, Abed-Navandi D, Paschinger K. Mol. Cell. Proteomics, 2016, 15(2): 573–597 [41] Schubert M, Walczak M J, Aebi M, Wider G. Angew. Chem. Int. Ed., 2015, 54(24): 7096–7100 [42] Wang Y G, Jing Y J, Leng F F, Wang S W, Wang F, Zhuang Y, Liu X F, Wang X L, Ma X Q. Sugar Tech, 2017, 19(4):
424–431 [43] Kandemir F M, Yuksel M, Ozdemir N, Deveci H. Vet. Arhiv, 2013, 83(6): 603–610 [44] Yang Y, Liu F, Franc V, Halim L A, Schellekens H, Heck A J. Nat. Commun., 2016, 7: 13397 [45] Souza B W S, Coimbra M A, Bourbon A I, Pinheiro A C, Martins J T, Teixeira J A, Coimbra M A, Vicente A A. Food Hydrocolloids, 2012, 27(2): 287–292 [46] Bie Z, Chen Y, Ye J, Wang S, Liu Z. Angew. Chem. Int. Ed., 2015, 54(35): 10211–10215 [47] Liu J, Chen C, Zhu R, Ye X, Jia J, Yang L, Wang Y, Wang W, Ye J, Li Y. Appl. Microbiol. Biot., 2015, 99(11): 4845–4853 [48] Huber W, Hurst J, Schlatter D, Barner R, Hübscher J, Kouns W C, Steiner B. Biosens. Bioelectron., 2010, 227(3): 647–656 [49] Okazaki I, Hasegawa Y, Shinohara Y, Kamasaki T, Bhikhabhai R. J. Mol. Recognit., 1995, 8(1-2): 95–99 [50] Stephenson-Brown A, Acton A L, Preece J A, Fossey J S, Mendes P M. Chem. Sci., 2015, 6(9): 5114–5119 [51] Ma X H, Li J P, Wang C, Xu G B. Chinese J. Anal. Chem., 2016, 44(1): 152–159 [52] Reuel N F, Mu B, Zhang J, Hinckley A, Strano M S. Chem. Soc. Rev., 2012, 41(17): 5744–5779 [53] Svarovsky S A, Joshi L. Anal. Methods, 2014, 6(12): 3918–3936 [54] Wei Q, Zhao Y, Xu C, Wu D, Cai Y, He J, Li H, Du B, Yang M. Biosens. Bioelectron., 2011, 26(8): 3714–3718 [55] Bertok T, Sediva A, Katrlik J, Gemeiner P, Mikula M, Nosko M, Tkac J. Talanta, 2013, 108(8): 11–18 [56] Belicky S, Černocká H, Bertok T, Holazova A, Réblová K, Paleček E, Tkac J, Ostatná V. Bioelectrochemistry, 2017, 117: 89–94 [57] Luna D M, Oliveira M D, Nogueira M L, Andrade C A. Chem. Phys. Lipids, 2014, 180(5): 7–14 [58] Avelino K Y P S, Andrade C A S, de Melo C P, Nogueira M L, Correia M T S, Coelho L C B B, Oliveira M D L. Synthetic Met., 2014, 194: 102–108 [59] Dai Z, Kawde A N, Xiang Y, LaBelle J T, Gerlach J, Bhavanandan V P, Joshi L, Wang J. J. Am. Chem. Soc., 2006, 128(31): 10018–10019 [60] Zhao L, Li C, Qi H, Gao Q, Zhang C. Sens. Actuators B, 2016, 235: 575–582 [61] Yang H, Li Z, Wei X, Huang R, Qi H, Gao Q, Li C, Zhang C. Talanta, 2013, 111(13): 62–68 [62] Pihikova D, Kasak P, Kubanikova P, Sokol R, Tkac J. Anal. Chim. Acta, 2016, 934: 72–79 [63] Silva M L S, Rangel M G H. Sens. Actuators B, 2017, 252: 777–784 [64] La Belle J T, Gerlach J Q, Svarovsky S, Joshi L. Anal. Chem., 2007, 79(18): 6959–6964 [65] Sadik O A, Yan F. Anal. Chim. Acta, 2007, 588(2): 292–296 [66] Klukova L, Filip J, Belicky S, Vikartovska A, Tkac J. Analyst, 2016, 141(14): 4278–4282 [67] Bertok T, Gemeiner P, Mikula M, Gemeiner P, Tkac J.
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
Microchim. Acta, 2013, 180(1-2): 151–159 [68] Hu Y, Zuo P, Ye B. Biosens. Bioelectron., 2013, 43(1): 79–83 [69] Vasapollop G, Del Sole R, Mergola L, Lazzoi M R, Scardino A, Scorrano S, Mele G. Int. J. Mol. Sci., 2011, 12(9): 5908–5945 [70] Li L, Lu Y, Bie Z J, Chen H Y, Liu Z. Angew. Chem. Int. Ed., 2017, 129(11): 2871 [71] Xing R R, Wang S S, Bie Z J, He H, Liu Z. Nat. Protoc., 2017, 12(5): 964–987 [72] Pinho S S, Reis C A. Nat. Rev. Cancer, 2015, 15(9): 540–555 [73] Li J, Ma X, Li M, Zhang Y. Biosens. Bioelectron., 2018, 99: 438–442 [74] Zhang Y, Wang F, Qian S, Liu Z, Wang Q, Gu Y, Wu Z, Jing Z, Sun C, Peng W. Sensors-Basel, 2017, 17(10): E2259 [75] Chen Y L, Liu H P, Ding L, Ju H X. Anal. Chem., 2018, 90(5): 3073–3078 [76] Geuijen K P M, Halim L A, Schellekens H, Schasfoort R B, Wijffels R H, Eppink M H. Anal. Chem., 2015, 87(16): 8115–8122 [77] Angeloni S, Ridet J L, Kusy N, Gao H, Crevoisier F, Guinchard S, Kochhar S, Sigrist H, Sprenger N. Glycobiology, 2005, 15(1): 31–41 [78] Ye J, Chen Y, Liu Z. Angew. Chem. Int. Ed., 2014, 53(39): 10386–10389 [79] Tu X Y, Muhammad P, Liu J, Ma Y Y, Wang S S, Yin D Y, Liu
Z. Anal. Chem., 2016, 88(24): 12363–12370 [80] Muhammad P, Tu X Y, Liu J, Wang Y J, Liu Z. ACS Appl. Mater. Interfaces, 2017, 9(13): 12082–12091 [81] Liu J, Yin D Y, Wang S S, Chen H Y, Liu Z. Angew. Chem. Int. Ed., 2016, 55(42): 13215–13218 [82] Bleher O, Schindler A, Yin M, Holmes A B, Luppa P B, Gauglitz G, Proll G. Anal. Bioanal. Chem., 2014, 406(14): 3305–3314 [83] Jiang T, Tan H, Sun Y, Wang J, Hang Y, Lu N, Yang J, Qu X, Hua J. Sens. Actuators B, 2018, 261: 115–126 [84] Pei Z C, Larsson R, Aastrup T, Anderson H, Lehn J M, Ramstrom O. Biosens. Bioelectron., 2006, 22(1): 42–48 [85] Zhang X, Zou Y, An C, Ying K, Chen X, Wang P. Sens. Actuators B, 2015, 217(10): 100–106 [86] Coulibaly F S, Youan B B C. Biosens. Bioelectron., 2014, 59: 404–411 [87] Yakovleva M E, Safina G R, Danielsson B. Anal. Chim. Acta, 2010, 668(1): 80–85 [88] Lu C, Zhang Y, Tang S, Fang Z, Yang H, Chen X, Chen G. Biosens. Bioelectron., 2012, 31(1): 439–444 [89] Zhou B, Hao Y, Long D, Yang P. Biosens. Bioelectron., 2018, 111: 90–96 [90] Chen J C, Sadhasivam S, Lin F H. Process. Biochem., 2011, 46(2): 543–550
Cite this article as: Chinese J. Anal. Chem., 2019, 47(9): 1283–1292
REVIEW
Research and Application of Glycoprotein Sensors Based on Glycosyl Recognition LIANG Jun-Yu, TONG Pei-Hong, LI Jian-Ping* College of Chemical and Bioengineering, Guilin University of Technology, Guangxi Key Laboratory of Electrochemical and Magnetochemical Function Materials, Guilin 541004, China
Abstract:
Glycoprotein is a binding protein whose structure is mainly determined by the content of sugars and proteins and the
peptide bonds to which it binds. There are many kinds of glycoproteins, and they can be classified into lectin, hormone, enzyme and immunoglobulin according to the clinical role in the medical field. Glycoproteins have a variety of biological functions and are of great significance in the medical and biological fields. In order to study the biological information related to glycoproteins, it is necessary to establish a highly sensitive and efficient analytical detection method for glycoproteins. The assay of glycoproteins includes separation and purification method, structural analysis and content determination. The commonly used methods for glycoproteins determination are mass spectrometry (MS), chromatography-mass spectrometry, surface excimer resonance, and enzyme-linked immunosorbent assay (ELISA), etc. In recent years, in the detection of glycoproteins, the research and application of sensors have gradually increased. This paper briefly summarized the analysis methods of glycoproteins and reviewed the research and application of glycoprotein biosensors based on glycosyl recognition. The glycoprotein biosensors including electrochemical sensors, optical sensors and mass sensors were introduced in detail. The future development direction of glycoprotein sensors was also prospected. Key Words:
Glycoprotein; Glycosyl; Sensors; Review
1 Introduction With the development of society and economy, the environment issues are becoming more and more serious, and human health is facing many threatens. Most diseases are caused by the lesion of human cells, such as tumors and cancer. Therefore, the timely and accurate diagnosis of diseases in early stage is of great significance for targeted clinical treatment and later rehabilitation[1]. In the process of cell changes, normal cells become uncontrolled malignant proliferating cells due to the action of carcinogenic factors, producing substances such as glycoproteins on the surface of cancer cells. Glycoproteins are closely related to the occurrence of various diseases and have been used as clinical biomarkers and therapeutic targets. Therefore, the analysis and
detection of glycoproteins is very important, and the development of rapid and accurate methods for the detection of glycoproteins has been widely concerned by researchers[2,3]. Glycoprotein is a kind of combinational protein, in which the composition of sugar contains a lot of structural information and can be used as the main specific recognition site. In the detection of glycoproteins, the characteristic glycosyl can be used for specific identification with lectins, antibodies or other molecules with glycosyl affinity. Glycoprotein biosensors have many advantages including high sensitivity, good selectivity and ease to use. This paper reviewed the research progress of glycoprotein analysis and glycoprotein biosensors based on glycosyl recognition.
2 Glycoprotein
________________________ Received 8 May 2019; accepted 18 June 2019 *Corresponding author. E-mail: [email protected] This work was supported by the National Natural Science Foundation of China (No. 21765006) and the Natural Science Foundation of Guangxi, China (No. 2015GXNSFFA139005). Copyright © 2019, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Published by Elsevier Limited. All rights reserved. DOI: 10.1016/S1872-2040(19)61185-0
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
Glycoproteins are widely presented in plants and animals, which are carriers of cell information. Glycoproteins are complex sugars composed of branched oligosaccharide chains covalently linked with polypeptide chains. Glycoproteins are widely distributed in nature, including 60 or 70 kinds of studied plasma proteins, some enzymes, hormones, and lectins isolated from plants or animals. Many early researches on sugar-protein interactions focused on identification of sugars by enzymes, such as endoglycosidase lysozyme which broke down cell walls of bacteria, and enzymes involved in intermediate metabolism. Fleming, Chain and Corey won the Nobel Prize in 1945 for discovering the antibacterial effects of lysozyme and penicillin. In the late 1960s, Phillips et al[4] obtained the three-dimensional structure of lysozyme from the complex formed by lysozyme and tetrasaccharide. In addition, other historic studies on the three-dimensional structure of glycoproteins are ConA (crystal structure of ConA was reported in 1972[5]) and hemagglutinin of influenza virus (crystal structure of ConA was reported in 1981 [6]). 2.1
Classification of glycoprotein
There are many kinds of glycoproteins. According to the type of peptide bond, they can be divided into o-connexin and n-connexin[7]. According to the differences in sugar and protein content in glycoproteins, they can be divided into proteoglycan[8] and glycoprotein[9]. The main difference between the two is that proteoglycan is mainly composed of glycan and assisted by protein, and the sugar content can reach 98%. Glycoproteins can be classified into soluble glycoproteins, membrane-bound glycoproteins and structural glycoproteins based on their existing state. Soluble glycoproteins include enzymes (e.g., nucleases, proteases, glycosidases), peptide hormones (e.g., chorionic gonadotropin, luteinizing hormone, thyrotropin, erythropoietin), antibodies, complement, and certain growth factors, interferons, statins, lectins and toxins. Membrane-bound glycoproteins include enzymes, receptors, lectins and carrier proteins. Structural glycoproteins include collagen and various non-collagen Table 1 Classification
Name
glycoproteins (fibronectin, laminin, etc.). There are many kinds of glycoproteins which exist widely in the body of organisms and are closely related to the growth of life. They have important research significance and clinical functions in the medical field, as shown in Table 1. 2.2
Clinical role of glycoproteins
Glycoprotein has important clinical significance. Glycoproteins include many indicators of clinical diagnosis or disease monitoring, which can not only provide information for clinical diagnosis, but also facilitate the judgment of recovery and interventional treatment. Glycoprotein-related diseases are represented by tumors, cancers and other diseases that cause great damage to the body. Zhou et al [22] established a enrichment strategy of glycoprotein based on sugar and lectin affinity, which was used in glycoprotein fucus glycosylation mass spectrum analysis. The results showed that the protein fucus glycosylation analysis helped to further understand the occurrence and development of prostate cancer, and provide effective reference basis for clinical judgment of invasion. In addition, glycoprotein also can be applied to the clinical diagnosis of pregnancy. For instance, high glycosylation human chorionic gonadotropin (hCG) is a related molecule of fluff gonadotropin hCG, which is secreted by undifferentiated or poorly differentiated cells of trophoblast cells. The rules of hCG protein skeleton structure is basically the same; the difference is that the modified sugar base ratio increased significantly in the process of expression of high glycosylation hCG, and the modified sugar-based molecular mass is bigger, with more complicated structure. High glycosylated hCG level is closely related to the development of early pregnancy and the occurrence and development of trophoblastic disease. Similar studies have been carried out in clinical diagnosis of animal pregnancy. de Rensis et al[23] improved the pregnancy rate of cows by using equine chorionic gonadotropin (eCG) for treatment and control of reproductive activities. Glycoproteins can also be used in clinical interventional therapy. Zhang et al[24] isolated and characterized a novel
Classification and role of glycoprotein Effect
Reference
Lectin
Animal lectin Plant lectin
Identification and adhesion of cells and molecules, such as tumor metastasis, etc.
[10] [11]
Hormone
Chorionic gonadotropin (CG) Follicle stimulating hormone (FSH) Luteinizing hormone (LH) Thyroid stimulating hormone (TSH)
It acts on specific tissues and organs, binds to the corresponding protein-coupled receptors, activates the secondary messenger pathway, promotes the release of glands, and plays an important regulatory role in growth and development.
[12] [13] [14] [15]
Enzyme
Lipoprotein lipase Tissue plasminogen activator Hyaluronidase Hepatic lipase
Participation in the body's metabolic system, it has the ability to improve the permeability of tissue fluid, enzyme activity as an indicator of clinical diseases such as leukemia, prostate tumors.
[16] [17] [18] [19]
Immunoglobulin
IgG/IgM/IgA/IgD/IgE
Complement activation, receptor binding, molecular recognition, molecular polymerization, etc.
[20] [21]
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
lectin with anti-tumor activity from red mushroom for the first time, which provided an effective idea for clinical treatment of tumor. In addition, one of the potential mechanisms of MDR is that the over-expression of p-glycoprotein (p-gp) in multidrug resistant cells increases the efflux of anticancer drugs. Li et al[25] ynthesized a soluble, water-soluble, single-walled carbon nanotube (anti-p-gp) antibody using MDR of p562 human leukemia cells, effectively overcoming multidrug resistance of human leukemia cells. Therefore, it is necessary to develop a simple and efficient method for glycoprotein detection.
3 Methods for glycoprotein analysis Glycoprotein analysis includes glycoprotein separation, structure analysis and identification, and content determination. Glycoprotein analysis is mainly based on the molecular size, shape, polarity, charge-to-mass ratio and intermolecular interaction. Single component glycoproteins are usually isolated from crude glycoproteins prior to glycoprotein analysis. 3.1
Separation and purification methods
The isolation and purification of glycoproteins, refers to the process of removing impurities from the crude glycoprotein products to obtain a single glycoprotein [26] is the basis of structural identification. Because lectin can recognize and bind to specific monosaccharide or sugar chain structure, immobilized lectin affinity chromatography[27] is the most commonly used method for isolation and purification of glycoproteins. Chromatographic separation technology usually mixes several methods to separate glycoproteins based on different molecular shapes and sizes and different charges of proteins in solutions with different pH values, including high performance liquid chromatography (HPLC), ion exchange chromatography, gel column chromatography and affinity chromatography. Electrophoretic separation is performed based on the characteristics of different charge loads of glycoproteins and different mobility under electric field [28]. Membrane separation is mainly a rough classification of glycoproteins with different molecular weights, which requires further separation by chromatography or electrophoresis. However, fractional precipitation method uses the differences in the size and solubility of glycoprotein molecules to achieve separation[29]. Borate affinity material (BAMs) has a unique affinity effect on cis-diol biomolecules, which can be used for selective separation and enrichment of sugars, glycosyl and glycoproteins. In recent years, it has also received more and more attention[30]. In the past, three major bottlenecks including non-biocompatible binding pH, weak affinity and selective operation difficulty existed in the practical application of BAMs. However, a variety of new
BAMs have emerged in recent years, which make the application prospect of BAMs broader[31]. Liu et al[32] proposed a variety of strategies, including the boron affinity lithography imprinting method based on boric acid affinity and highly specific molecular imprinting technology, and the boron affinity controllable directional imprinting method, which solved the above problems well and effectively improved the affinity and selectivity of BAMs. 3.2
Structural analysis methods
At present, the structural analysis methods of glycoproteins include methylation analysis[33], iodine oxidation[34], nuclear magnetic resonance (NMR)[35], chromatography-MS[36], x-diffraction[37], etc., mainly involving molecular weight, polysaccharide and protein content, amino acid composition and sequence, sugar chain structure and other molecular information[38]. The information of sugar chain structure is essential in the analysis of glycoprotein structure, including monosaccharide composition, connection mode and branch structure. Generally, such information is obtained through release of sugar chain. Currently, the release of n-sugar chain adopts the enzymatic hydrolysis method [39], such as endoglycosidase, trypsin, etc. O-sugar chain is released by chemical method, such as beta-elimination method[40]. The primary structure of polysaccharides can be identified by HPLC, NMR and MS. High-resolution NMR technology can study the three-dimensional structure of sugar chains, and express structural characteristics through chemical displacement, integral area, coupling constant and other information[41]. The MS method is mainly used for the analysis of sugar chain structure, including electrospray ionization MS (ESI-MS), matrix-assisted laser-desorption time-of-flight MS (MALDI-TOF-MS) and fast atom bombardment MS, etc., which can be used for the analysis of connection mode of sugar peptide bonds and glycosylation sites. 3.3
Methods for determination of sugar and protein content
The determination of polysaccharide content is usually based on the reducibility of sugar, such as phenol-sulfuric acid method[42]. In the determination of protein content, proteins are usually combined with dyes to form compounds, and the content is determined according to the color depth, such as the forinol method[43]. The molecular weight and isoelectric point of glycoprotein samples can be quickly identified by gel filtration chromatography or polyacrylamide gel electrophoresis. Secondly, the structural information of amino acids in proteins can be determined by ion exchange chromatography, HPLC and capillary electrophoresis. In addition, the specificity of characteristic glycosyl or
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
sugar chain in glycoproteins is the focus of analysis and detection. The common detection method of glycoproteins is MS method[44], and the combination method of LC and MS has attracted more and more attention[45]. However, these methods have some disadvantages, such as high cost of instrument, requirement of professional skills of operators and complex pretreatment of samples. Therefore, it is of great significance to develop a mild and efficient method for the isolation and detection of glycoproteins. Chip method solves these issues very well. Instead of releasing the sugar chain from the glycoprotein, chip method can directly detect the sugar chain of the glycoprotein[46]. Chip methods include surface exciton resonance, enzyme-linked immunosorbent assay[47] and biosensors[48]. The detection principle of this method is to fix monosaccharide, lectin[49] and antibody on the matrix, which specifically bind to glycoproteins to generate detection signals. Biosensors are the most widely used biosensors, and the combination of sensor technology to prepare glycoprotein biosensors can quickly, effectively and sensitively detect glycoprotein molecules qualitatively and quantitatively[50].
4
Classification and application of glycoprotein sensors for glycosyl recognition
Biosensors are a very active research field at present, the focus of which is to develop bioactive materials that can be used as sensitive elements, such as biological macromolecules[51]. Since the 1980s, researches on biosensors including glycoprotein biosensors have attracted more and more attention, and glycoprotein biosensors using antibodies, hormones, receptors, molecularly imprinted membranes and other recognition elements have been developed. At present, biosensors are in the early stage of detecting glycan and lectin. So far, the most commonly used method in carbohydrate biosensors is to detect carbohydrate compounds based on a series of lectin/carbohydrate identification on lectin array[52]. Lectin arrays have been used effectively to analyze glycoproteins as well as proteoglycans on the surface of bacterial and mammalian cells. The characteristic glycosyl or sugar chain of glycoproteins is the key to the selective recognition of glycoproteins by sensors. In addition, the Table 2 Glycoprotein target Carcinoembryonic antigen(CEA)
glycoprotein sensors with high sensitivity and low detection limit can be developed by combining catalytic effect or doping nanomaterials and other sensitization methods[53]. There are many kinds of sensors based on glycosyl-based glycoprotein recognition. According to the signal conversion type, sensors can be divided into electrochemical type, optical type and mass type. 4.1
Electrochemical sensors
The sugar moiety recognition-based electrochemical sensors of glycoproteins which combines the high sensitivity of electrochemical detection method and the inherent biological selectivity of glycoprotein molecules can selectively identify the targets by specific recognition of the glycogroup or sugar chain of glycoproteins based on the generating electrical signals, so as to realize qualitative or quantitative detection. Currently, electrochemical sensors are widely used as a kind of glycoprotein biosensors [54,55], which can be divided into current type, impedance type and potential type[56]. Most of them are current type and impedance type. Some researches on glycoprotein sensors based on lectin specific recognition of sugar groups are listed in Table 2. Among them, the current mode is through modification with lectin or carbohydrate recognition elements such as molecularly imprinted membrane electrode, and the electroactive probe electron will transfer on the electrode surface when the glycoprotein molecules are specifically bound on the electrode surface. With adsorption of different concentrations of target glycoprotein molecule, the electron transfer rate changes on the surface of the electrode, resulting in the changes in current[57]. The carbohydrate recognitionbased glycoprotein impedance type sensors is to use lectins and specific binding of sugar-based sugar chain, in the process of detection, because the heavy adsorption moleculars hinder the electron transfer of electroactive probe on the sensor surface, the impedance value of the sensors shows a certain linear relationship with glycoprotein concentration, so as to realize the quantitative and qualitative test of glycoprotein[58,59]. The detection sensitivity of EIS sensors can be improved by adding sensitizing material. Common sensitizers include
List of glycoprotein electrochemical sensors based on lectin-specific glycosylation Output signal Current
Lectin
Detection range –1
Limit of detection –1
Reference
Concanavalin A (ConA)
1–10 ng mL
0.03 ng mL
[60]
Wheat germ agglutinin (WGA)
1–100 ng mL–1
0.1 ng mL–1
[61]
Sambucus nigra lection (SNA)
100 μg/mL
100 ag mL–1
[62]
0.68 g mL–1
[63]
> 1 g mL–1
1 pg mL–1
[64]
1–1105 ng mL–1
1 ng mL–1
[65]
Electrochemical Alpha fetoprotein (AFP)
Impedance Spectroscopy (EIS)
Prostate specific antigen (PSA)
EIS
Fetuin (FET)
EIS
Vicia villosa lectin (VVA)
Fetuin (FET)
EIS
Peanut agglutinin (PNA)
Antigens (ProBL)
Current
WGA
–1
> 2.25 g mL
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
AuNPs with high conductivity and biocompatibility, graphene and carbon nanotubes with high electron transfer rate, and metal-organic frame materials with high specific surface area and frame stability. Klukova et al[66] prepared an impedance sugar-based recognition sensors based on the specific recognition of ConA toward mannose. To further improve the sensitivity of the sensors, they took advantage of the high conductivity of graphene oxide (GO) modified on the surface of the electrode to increase the electron transfer rate. In addition, some lectins have strong affinity to glycosyl groups. Bertok et al[67] prepared a ultrasensitive label-free agglutinin EIS biosensor based on strong specificity of SNA I toward glycoprotein-fetoglobulin containing sialic acid sugar group. The detection range covered 7 orders of magnitude, and the detection limit was lower than 0.54 fM (Fig.1). Hu et al[68] developed a new type of EIS sensor by modifying ConA that could specially identify mannose on the gold electrode on the basis of the interaction of carbohydrates and lectin. This sensor could be used to directly identify mannose glycoprotein on the surface of the cancer cells or sugar peptide, and was successfully applied to the detection of liver cancer cells (Fig.2). Molecular imprinting technology[69] has the characteristics of structure-activity reservation, environmental tolerance and high selectivity, and is a good development direction to apply
Fig.1
Fig.2
molecular imprinting technology to the detection of glycoproteins. In the past few years, the imprinting of biological macromolecules has been very challenging, especially for proteins. This is because the large size of proteins makes it difficult to remove them from highly crosslinked polymer networks, leading to great obstacles in the research and application of glycoprotein imprinting sensors. Liu et al[70] proposed an imprinting strategy that combined the affinity of borate with the advantages of molecular imprinting sensors, namely, photolithography of borate affinity molecular imprinting. In this work, the glycoprotein template and monomer formed covalent compounds by borate affinity function, and the boric acid complex was polymerized with crosslinking agent under UVlight irradiation. By simply adjusting solution pH value, the imprinted cavity was obtained. This strategy had good biological compatibility in a wide pH range, strong affinity, high specificity and good anti-jamming capability. However, this method had some limitations. For example, it required that the substrate must be able to accept ultraviolet radiation to generate polymerization. Therefore, the team further developed another simple and more universal method, namely, controllable directional surface imprinting based on the affinity of borates[71]. In addition, inspired by the antigendetermining imprinting method and combined with the
Schematic of an ultrasensitive label-free lectin impedance biosensors[67]
Schematic diagram of EIS biosensor based on interaction of carbohydrates and lectins [68]
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
glycation alteration behavior of the tumor[72], our research group[73] proposed a new macromolecular imprinting strategy based on glycation, which used the characteristic glycosyl of tumor markers as the imprinting template to recognize the whole glycoprotein macromolecule. As shown in Fig.3, the polysaccharide molecularly imprinted sensors were successfully prepared with the sugar-based slea structure featured by excessive expression at the end of the sugar antigen CA19-9 as template molecule and o-phenylendiamine as functional monomer. By using potassium ferricyanide as ion probe, the prepared sensors were applied to the quantitative detection of CA19-9 in concentration range of 0.1–5 U mL–1 by indirect method, with a detection limit of 0.028 U mL–1. The prepared imprinting sensors also effectively solved the difficulty of large molecular imprinting of glycoproteins. Compared with traditional immunoassay, the sensors had many advantages including low cost, simple and rapid preparation. This study provided a non-immunoassay
Fig.3
Fig.4
method for the detection of glycoproteins with high sensitivity, selectivity, convenience, efficiency and applicability. 4.2
Optical sensors
The optical sensors that can detect glycoproteins by identifying glycosyl groups are usually based on surface plasmon resonance (SPR) [74], fluorescence [75] and other principles to directly or indirectly obtain the changes of optical signals, thus achieving the detection of analyte. The SPR sensors do not need to be labeled, and the biospecific interaction occurs directly on the surface of the sensors chip. Based on SPR technology and specific affinity of ConA and SNA on mannose and fucose, Geuijen et al[76] built a multiple SPR imaging platform for specificity recognition of sugar-based glycoprotein characteristics of lectin, which provided an important reference (Fig.4) for unmarked immunoassay of glycoprotein. In addition, Angeloni et al[77]
Construction of CA19-9 electrochemical sensor based on glycosylation change[73]
Construction of label-free detection of lectin-glycosyl sensors based on surface plasmon resonance[76]
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
made use of the specific recognition effect of lectin and sugar chain components to modify lectin on the surface of glass slides. Based on this, they prepared fluorescence sensors through fluorescence labeling and other detection methods for the efficient analysis of sugar chain structure of glycoproteins on the surface of living cells. In recent years, based on the covalent bonding between boric acid and sugar, high specificity of molecularly imprinted polymers and surface enhanced Raman scattering technique, etc., Liu et al put forward two new optical sensing methods, boron affinity sandwich method (BASA)[78] and plasma immune sandwich method (PISA)[79–81], for determination of trace amounts of glycoprotein in complex samples. The prepared sensors had rapid detection speed and high sensitivity, showing broad application prospects. Fluorescent probes play an indispensable role in the study of optical sensors for detection of glycoproteins. Because fluorescent probe binds with antigens and antibodies and does not affect their activity, it is usually used for labeling antigens and antibodies in glycoprotein fluorescence immunoassay[82]. However, it is generally difficult to obtain specific antibodies and the cost is high. Jiang et al[83] synthesized two new sugar-based fluorescent probes, PT-Man and PT-Gal, based on the interaction between sugar and lectin, and further improved the sensitivity of the sensors by using GO as a sugar base platform (the detection limit reached 10‒9 M, Fig.5). This method provided a reference basis for the study of the acceptor reaction between cell, known or unknown. 4.3
Quality sensors
The quality sensors include quartz crystal microbalances (QCM) sensors[84] and surface acoustic wave sensors[85], etc. In general, the changes of parameters of the surface of the
Fig.5
sensors material, such as piezoelectric or pressure, can directly result in the quality signal change, which can be converted to electrical signals or directly calculate quality signal changes value. Therefore, the quantitative analysis can be performed according to the linear relationship of the change of quality signal value and the analyte concentration. At present, the carbohydrate recognition-based sensors[86,87], which are mainly combined with QCM design for analysis, are prepared by fixing the sugar-based lectin with specific recognition on the surface of the functionalized sensors platform. Because the quality signal of sensing platform changes with the change of resonance frequency in a certain proportion, the quantitative detection of glycoprotein can be achieved. Based on epitope imprinting technology, Lu et al[88] developed a new type of sensor by polymerization of imprinted film on the surface of QCM with dopamine as the functional monomer and HIV-1 glycoprotein fragments of synthetic peptide as template molecule. This sensor not only had a strong affinity for template peptide, but also could specifically detect HIV surface glycoprotein GP41, with a detection limit of 2 ng mL–1 (Fig.6). Compared with the conventional enzyme-linked immunoassay, the sensor had a better practical analysis performance. In addition, it could also be used for sensitive detection of cells[89] and antigens[90].
5
Conclusions and prospects
Glycoproteins have complex biological structural information and can directly or indirectly participate in biomolecular recognition. Compared with the traditional MS method, the glycoprotein sensors with high specificity and high sensitivity constructed by using glycosimprinting and boric acid affinity imprinting have the characteristics of rapid detection and high sensitivity, which is an ideal development direction for
Schematic diagram of fluorescent sensor constructed by novel glycosyl fluorescent probe [83]
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
Fig.6
Schematic diagram of detection of HIV-associated glycoprotein by surface-imprinted quartz crystal microbalance[88]
glycoprotein research. Borate affinity molecular imprinting membrane or glycolic imprinting membrane was used to construct glycoprotein sensors with high specificity, convenience and efficiency. On the other hand, it makes up for the shortage of template molecules that are difficult to elute in the study of glycoprotein imprinting in the past. In addition, the specific binding of lectin and glycosyl can be used to further expand the research field of glycosyl sensors. At present, glycoprotein biosensors are in the rapid development stage, and some researchers have achieved commercial promotion and application, such as pregnancy test stick, providing reliable reference for early detection and timely treatment of related diseases in the detection and analysis of tumor markers. With the development of life analytical science, glycoprotein biosensors based on glycosylation recognition still have great space for improvement. They can be applied to the research of cells, viruses and even individuals with vital signs by combining new nanomaterials and imaging technologies, which will be the research direction in the future.
Chinese J. Chromatogr., 2018, 36(12): 1197–1205 [4]
Phillips D C. Sci. Am., 1966, 215(5): 78–93
[5]
Hardman K D, Ainsworth C F. Biochemistry, 1972, 11(26): 4910–4919
[6]
Wilson I A, Skehel J J, Wiley D C. Nature, 1981, 289(5796):
[7]
Jensen P H, Karlsson N G, Kolarich D, Packer N H. Nat.
366–373 Protoc., 2012, 7(7): 1299–1310 [8]
Merkle R K, Poppe I. Methods Enzymol., 1994, 230(4): 1–15
[9]
Alexander S P, Benson H E, Faccenda E, Pawson A J, Sharman J L, Speding M, Peter J A, Harmar A J. Brit. J. Pharmacol., 2014, 170(8): 1459–1581
[10] Stern D, Pauly D, Zydek M, Müller C, Avondet M A, Worbs S, Lisdat F, Dorner M B, Dorner B G. Biosens. Bioelectron., 2015, 78: 111–117 [11] Toshima T, Shirabe K, Ikegami T, Yoshizumi T, Kuno A, Togayachi A, Gotoh M, Narimatsu H, Korenaga M, Mizokami M. J. Gastroenterol., 2015, 50(1): 76‒84 [12] Diana T, Krause J, Olivo P D, König J, Kanitz M, Decallonne B, Kahaly G J. Clin. Exp. Immunol., 2017, 189(3): 304–309 [13] Pocius K D, Maurer R, Fortin J, Goldberg A B, Bartz D.
References
Contraception, 2015, 91(6): 503–506 [14] Santi D, Casarini L, Alviggi C, Simoni M. Front. Endocrinol.,
[1]
Kreicbergs U, Valdimarsdóttir U, Steineck G, Henter J I. Lancet, 2004, 364(9436): 787–789
[2]
Beck W T, Grogan T M, Willman C L, Cordoncardo C, Parham D M, Kuttesch J F, Andreeff M, Bates S E, Berard C W, Boyett
2017, 8: 114 [15] Vestergaard E T, Schjørring M E, Kamperis K, Petersen K K, Rittig S, Juul A, Kritstensen K, Birkebæk N H. Eur. J. Endocrinol., 2017, 176(6): 747–753
J M, Brophy N A, Broxterman H J, Chan H S, Dalton W S,
[16] Calderon R M, Diaz S, Szeto A, Llinas J A, Hughes T A,
Dietel M, Fojo A T, Gascoyne R D, Head D, Houghton P J,
Mendez A J, Goldberg R B. J. Clin. Endocr. Metab., 2015,
Srivastava D K, Lehnert M, Leith C P, Paietta E, Pavelic Z P, Weinstein R. Cancer Res., 1996, 56(13): 3010–3020 [3] Zhao Y, Zhang Y, Wang M C, Meng B, Ying W T, Qian X H.
100(7): 2581–2588 [17] Gong H, Chao Y, Xiang J, Han X, Song G, Feng L, Liu J, Yang G, Chen Q, Liu Z. Nano Lett., 2016, 16(4): 2512‒2521
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
[18] Moore H B, Moore E E, Gonzalez E, Hansen K C, Dzieciatkowska M, Chapman M P, Sauaia A, West B, Banerjee A, Silliman C C. Shock, 2015, 43(1): 39–46 [19] Reiner Ž, Guardamagna O, Nair D, Soran H, Hovingh K, Bertolini S, Jones S, Ćorić M, Calandra S, Hamilton J, Eagleton T, Ros E. Atherosclerosis, 2014, 235(1): 21–30 [20] Liang L, Willis-Owen S A, Laprise C, Wong K C, Davies G A, Hudson T J, Binia A, Hopkin J M, Yang I V, Grundberg E, Busche S, Hudson M, Rnnblom L, Pastinen T, Schwartz D A, Lathrop G M, Moffatt M F, Cookson W O. Nature, 2015, 520(7549): 670–674 [21] Walker B A, Wardell C P, Brioli A, Boyle E, Kaiser M F, Begum D B, Dahir N B, Johnson D C, Ross F M, Davies F E. Blood Cancer J., 2014, 4(3): e191 [22] Zhou J, Yang W, Hu Y, Höti N, Liu Y, Shah P, Sun S, Clark D, Thomas S, Zhang H. Anal. Chem., 2017, 89(14): 7623–7630 [23] de Rensis F, López-Gatius F. Reprod Dom. Anim., 2014, 49(2): 177–182 [24] Zhang G, Sun J, Wang H, Ng T B. Phytomedicine, 2010, 17(10): 775–781 [25] Li R, Wu R, Zhao L, Wu M, Yang L, Zou H. ACS Nano, 2010, 4(3): 1399–1408 [26] Ugozzoli M, Chiu A. Biotechniques, 1992, 12(2):187–190 [27] Meiniger M, Stepath M, Henning R, Cajic S, Rapp E, Rotering H, Wolff M W, Reichl U. J. Chromatogr. B, 2016, 1012-1013: 193–203 [28] Cong W, Zhou A, Liu Z, Shen J, Zhou X, Ye W, Zhu Z, Zhu X, Lin J, Jin L. Anal. Chem., 2015, 87(3): 1462–1465 [29] Arnold L, Chen R. Biotechnol. Bioeng., 2014, 111(2): 413–417 [30] Nishiyabu R, Kubo Y, James T D, Fossey J S. Chem. Commun., 2011, 47(4): 1106–1123 [31] Li D J, Chen Y, Liu Z. Chem. Soc. Rev., 2015, 44(22): 8097–8123 [32] Liu Z, He H. Accounts Chem. Res., 2017, 50(9): 2185–2193 [33] Shajahan A, Supekar N T, Heiss C, Ishihara M, Azadi P. Anal. Chem., 2017, 89(20): 10734–10743 [34] Giannini G, Alekseeva A, Naggi A, Salvini L, Tei L, de Santis R. Anal. Bioanal. Chem., 2018, 410(2): 553–564 [35] Gallo M, Matteucci S, Alaimo N, Pitti E, Orsale M V, Summa V, Cicero D O, Monteaqudo E. J. Pharm. Anal., 2019, 167: 21–29 [36] Huang Y L, Jhou B Y, Chen S F, Khoo K H. Anal. Sci., 2018, 34(9): 1049–1054 [37] Kent S B H. Protein Sci., 2019, 28(2): 313–328 [38] HofbauerováK, Jr K V, Sýkora J, Karpenko V. Biophys. Chem., 2003, 103(1): 25–33 [39] Yan J P, Liu Y R, Wang K X, Li D Y, Hu Q Q, Zhang W J. Plant Sci., 2018, 276: 143–151 [40] Eckmair B, Jin C S, Abed-Navandi D, Paschinger K. Mol. Cell. Proteomics, 2016, 15(2): 573–597 [41] Schubert M, Walczak M J, Aebi M, Wider G. Angew. Chem. Int. Ed., 2015, 54(24): 7096–7100 [42] Wang Y G, Jing Y J, Leng F F, Wang S W, Wang F, Zhuang Y, Liu X F, Wang X L, Ma X Q. Sugar Tech, 2017, 19(4):
424–431 [43] Kandemir F M, Yuksel M, Ozdemir N, Deveci H. Vet. Arhiv, 2013, 83(6): 603–610 [44] Yang Y, Liu F, Franc V, Halim L A, Schellekens H, Heck A J. Nat. Commun., 2016, 7: 13397 [45] Souza B W S, Coimbra M A, Bourbon A I, Pinheiro A C, Martins J T, Teixeira J A, Coimbra M A, Vicente A A. Food Hydrocolloids, 2012, 27(2): 287–292 [46] Bie Z, Chen Y, Ye J, Wang S, Liu Z. Angew. Chem. Int. Ed., 2015, 54(35): 10211–10215 [47] Liu J, Chen C, Zhu R, Ye X, Jia J, Yang L, Wang Y, Wang W, Ye J, Li Y. Appl. Microbiol. Biot., 2015, 99(11): 4845–4853 [48] Huber W, Hurst J, Schlatter D, Barner R, Hübscher J, Kouns W C, Steiner B. Biosens. Bioelectron., 2010, 227(3): 647–656 [49] Okazaki I, Hasegawa Y, Shinohara Y, Kamasaki T, Bhikhabhai R. J. Mol. Recognit., 1995, 8(1-2): 95–99 [50] Stephenson-Brown A, Acton A L, Preece J A, Fossey J S, Mendes P M. Chem. Sci., 2015, 6(9): 5114–5119 [51] Ma X H, Li J P, Wang C, Xu G B. Chinese J. Anal. Chem., 2016, 44(1): 152–159 [52] Reuel N F, Mu B, Zhang J, Hinckley A, Strano M S. Chem. Soc. Rev., 2012, 41(17): 5744–5779 [53] Svarovsky S A, Joshi L. Anal. Methods, 2014, 6(12): 3918–3936 [54] Wei Q, Zhao Y, Xu C, Wu D, Cai Y, He J, Li H, Du B, Yang M. Biosens. Bioelectron., 2011, 26(8): 3714–3718 [55] Bertok T, Sediva A, Katrlik J, Gemeiner P, Mikula M, Nosko M, Tkac J. Talanta, 2013, 108(8): 11–18 [56] Belicky S, Černocká H, Bertok T, Holazova A, Réblová K, Paleček E, Tkac J, Ostatná V. Bioelectrochemistry, 2017, 117: 89–94 [57] Luna D M, Oliveira M D, Nogueira M L, Andrade C A. Chem. Phys. Lipids, 2014, 180(5): 7–14 [58] Avelino K Y P S, Andrade C A S, de Melo C P, Nogueira M L, Correia M T S, Coelho L C B B, Oliveira M D L. Synthetic Met., 2014, 194: 102–108 [59] Dai Z, Kawde A N, Xiang Y, LaBelle J T, Gerlach J, Bhavanandan V P, Joshi L, Wang J. J. Am. Chem. Soc., 2006, 128(31): 10018–10019 [60] Zhao L, Li C, Qi H, Gao Q, Zhang C. Sens. Actuators B, 2016, 235: 575–582 [61] Yang H, Li Z, Wei X, Huang R, Qi H, Gao Q, Li C, Zhang C. Talanta, 2013, 111(13): 62–68 [62] Pihikova D, Kasak P, Kubanikova P, Sokol R, Tkac J. Anal. Chim. Acta, 2016, 934: 72–79 [63] Silva M L S, Rangel M G H. Sens. Actuators B, 2017, 252: 777–784 [64] La Belle J T, Gerlach J Q, Svarovsky S, Joshi L. Anal. Chem., 2007, 79(18): 6959–6964 [65] Sadik O A, Yan F. Anal. Chim. Acta, 2007, 588(2): 292–296 [66] Klukova L, Filip J, Belicky S, Vikartovska A, Tkac J. Analyst, 2016, 141(14): 4278–4282 [67] Bertok T, Gemeiner P, Mikula M, Gemeiner P, Tkac J.
LIANG Jun-Yu et al. / Chinese Journal of Analytical Chemistry, 2019, 47(9): 1283–1292
Microchim. Acta, 2013, 180(1-2): 151–159 [68] Hu Y, Zuo P, Ye B. Biosens. Bioelectron., 2013, 43(1): 79–83 [69] Vasapollop G, Del Sole R, Mergola L, Lazzoi M R, Scardino A, Scorrano S, Mele G. Int. J. Mol. Sci., 2011, 12(9): 5908–5945 [70] Li L, Lu Y, Bie Z J, Chen H Y, Liu Z. Angew. Chem. Int. Ed., 2017, 129(11): 2871 [71] Xing R R, Wang S S, Bie Z J, He H, Liu Z. Nat. Protoc., 2017, 12(5): 964–987 [72] Pinho S S, Reis C A. Nat. Rev. Cancer, 2015, 15(9): 540–555 [73] Li J, Ma X, Li M, Zhang Y. Biosens. Bioelectron., 2018, 99: 438–442 [74] Zhang Y, Wang F, Qian S, Liu Z, Wang Q, Gu Y, Wu Z, Jing Z, Sun C, Peng W. Sensors-Basel, 2017, 17(10): E2259 [75] Chen Y L, Liu H P, Ding L, Ju H X. Anal. Chem., 2018, 90(5): 3073–3078 [76] Geuijen K P M, Halim L A, Schellekens H, Schasfoort R B, Wijffels R H, Eppink M H. Anal. Chem., 2015, 87(16): 8115–8122 [77] Angeloni S, Ridet J L, Kusy N, Gao H, Crevoisier F, Guinchard S, Kochhar S, Sigrist H, Sprenger N. Glycobiology, 2005, 15(1): 31–41 [78] Ye J, Chen Y, Liu Z. Angew. Chem. Int. Ed., 2014, 53(39): 10386–10389 [79] Tu X Y, Muhammad P, Liu J, Ma Y Y, Wang S S, Yin D Y, Liu
Z. Anal. Chem., 2016, 88(24): 12363–12370 [80] Muhammad P, Tu X Y, Liu J, Wang Y J, Liu Z. ACS Appl. Mater. Interfaces, 2017, 9(13): 12082–12091 [81] Liu J, Yin D Y, Wang S S, Chen H Y, Liu Z. Angew. Chem. Int. Ed., 2016, 55(42): 13215–13218 [82] Bleher O, Schindler A, Yin M, Holmes A B, Luppa P B, Gauglitz G, Proll G. Anal. Bioanal. Chem., 2014, 406(14): 3305–3314 [83] Jiang T, Tan H, Sun Y, Wang J, Hang Y, Lu N, Yang J, Qu X, Hua J. Sens. Actuators B, 2018, 261: 115–126 [84] Pei Z C, Larsson R, Aastrup T, Anderson H, Lehn J M, Ramstrom O. Biosens. Bioelectron., 2006, 22(1): 42–48 [85] Zhang X, Zou Y, An C, Ying K, Chen X, Wang P. Sens. Actuators B, 2015, 217(10): 100–106 [86] Coulibaly F S, Youan B B C. Biosens. Bioelectron., 2014, 59: 404–411 [87] Yakovleva M E, Safina G R, Danielsson B. Anal. Chim. Acta, 2010, 668(1): 80–85 [88] Lu C, Zhang Y, Tang S, Fang Z, Yang H, Chen X, Chen G. Biosens. Bioelectron., 2012, 31(1): 439–444 [89] Zhou B, Hao Y, Long D, Yang P. Biosens. Bioelectron., 2018, 111: 90–96 [90] Chen J C, Sadhasivam S, Lin F H. Process. Biochem., 2011, 46(2): 543–550