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Overview and Introduction
6.01 Overview and Introduction Robert Woodward and Peng George Wang, The Ohio State University, Columbus, OH, USA ª 2010 Elsevier Ltd. All rights reserved.
6.01.1 6.01.2
Introduction Overview
1 1
6.01.1 Introduction Given the prevalence of sugars in nature, it is no surprise that a thorough understanding of carbohydrate chemistry coupled with glycobiology is often essential to elucidating the details of complex biological processes such as polysaccharide biosynthesis, the glycosylation of proteins in both prokaryotic and eukaryotic cells, and glycoconjugate-induced immunological activity. This has enabled the extension of previously existing synthetic strategies, as well as the development of novel methods, for the preparation of complicated carbohydratebased biomolecules. For example, many excellent organometallic transformations have found applicability in glycoconjugate chemistry. Furthermore, the advance of physical organic chemistry has yielded a deeper understanding of the mechanism of glycosylation reactions, consequently allowing several new glycosylation approaches to be developed. These advances, coupled with those made in biology and biotechnology, have thus further solidified the necessity of effectively interweaving chemistry and biology. It is here, where chemistry and biology meet, that many more breakthroughs across various disciplines will undoubtedly be made.
6.01.2 Overview The 20 additional chapters that comprise this volume provide a detailed look at carbohydrates and their uses both in a laboratory setting and in nature, while also examining a variety of other important biomolecules and associated processes. The first three chapters, contributed by Peng George Wang, Ashraf Brik, and Zhongwu Guo, consider how carbohydrates can be utilized for synthetic purposes. Both enzymatic and chemical modes of synthesis are discussed with regard to their use for complex carbohydrate, glycoprotein, and vaccine production. Applications of mass spectrometry to analysis of glycans are then explored in the next two chapters as authors Kay-Hooi Khoo and Jianjun Li discuss some of the more advanced technologies in the field. Chapters 6.07–6.09 offer a look at the burgeoning field of chemical glycobiology. A broad look at this area is first presented by Jennifer Kohler in Chapter 6.07 with topics ranging from chemoenzymatic approaches to understanding glycan structure and function to the use of photocross-linkers for the covalent trapping of interactions between glycans. The final two chapters of this section, written by Alan Elbein and Howard Hang, take a more focused approach, considering how certain processes can be studied through the use of inhibitors and probes. The next section of this volume introduces how carbohydrates are utilized in a variety of biosynthetic pathways. Specifically, author Miguel Valvano first considers O-antigen biosynthesis, a process that is essential in the production of lipopolysaccharide. A discussion of the generation of glycoproteins in both mammalian and bacterial systems follows in the next two chapters with contributions from Inka Brockhousen and Mario Feldman. Subsequently, the structure and biosynthesis of the mycobacterial cell wall and glycosaminoglycans are examined by Dean Crick and Jian Liu in Chapters 6.13 and 6.14, respectively. The reader is then offered a section by Jack Preiss, which details the processes of bacterial and mammalian glycogen biosynthesis, while also examining the production of starch in plants. Finally, Rajai Atalla’s contribution, Chapter 6.16, focuses upon celluloses and their various roles in nature. In the closing chapters of this volume, a variety of other important biomolecules and related processes are highlighted. Specifically, Norman Lewis and Daneel Ferreira describe lignins and proanthocyanidins in Chapters 6.17 and 6.18, specifically looking at the chemistry and biology of these highly aromatic molecules. 1
2 Overview and Introduction
The final three chapters then direct attention to the areas of DNA and RNA with Darrell Davis first illustrating the importance and utility of nucleoside analogs. Chapter 6.20, written by George Garcia, subsequently examines how RNA is modified enzymatically and the corresponding consequences thereof before the structures and roles of riboswitches in regulatory processes are presented by Tina Henkin in Chapter 6.21. As is quite apparent, the topics that appear within this volume vary quite extensively. However, whether it is a discussion of the transfer of an oligosaccharyl moiety to a serine residue in O-glycosylation or the regulation of transcription termination through a riboswitch, it is hoped that the reader will not only come away with an appreciation for all of the biomolecules discussed, but more importantly recognize the diversity of processes that these small molecules and associated polymers can perform and/or regulate.
Biographical Sketches
Robert Woodward obtained a B.A. in chemistry (2006) and a B.S. in biology (2006) from The Ohio State University. He is an NIH Chemistry–Biology Interface Program Predoctoral Fellow currently pursuing a Ph.D. in organic chemistry at The Ohio State University. His research focuses on the applications of synthesis for studying complex biological processes such as polysaccharide biosynthesis and oligosaccharide transfer.
Peng George Wang obtained a B.S. in chemistry (1984) from Nankai University, China, and a Ph.D. in organic chemistry (1990) from the University of California, Berkeley. He then conducted postdoctoral research at the Scripps Research Institute before becoming an assistant professor in 1994 at the University of Miami in Coral Gables. From 1997 to 2003, he was a faculty member at Wayne State University. Since then, he has served in the Departments of Biochemistry and Chemistry at The Ohio State University as Ohio Eminent Scholar in Macromolecular Structure and Function.
Overview and Introduction 3
Research in the Wang laboratory is predominately focused on four areas of glycoscience. Glycochemistry: Work is centered on the generation of uncommon sugar libraries as well as the synthesis of key intermediates in carbohydrate-based biological processes, which are essential for their study. Glycobiology: Biochemical characterization of carbohydrate-active enzymes and investigations of the biological functions of carbohydrates in human diseases, immunity, and general microbiology are performed. Glycotechnology: Biosynthetic pathways are engineered for the synthesis of glycopharmaceuticals, polysaccharides for vaccine development, and biomedically important human glycoproteins. Glycoanalysis: Analysis of carbohydrate composition, sequence, structure, and their interaction with proteins through MS, NMR, QCM, and other analytical methods is conducted.
6.01.1 6.01.2
Introduction Overview
1 1
6.01.1 Introduction Given the prevalence of sugars in nature, it is no surprise that a thorough understanding of carbohydrate chemistry coupled with glycobiology is often essential to elucidating the details of complex biological processes such as polysaccharide biosynthesis, the glycosylation of proteins in both prokaryotic and eukaryotic cells, and glycoconjugate-induced immunological activity. This has enabled the extension of previously existing synthetic strategies, as well as the development of novel methods, for the preparation of complicated carbohydratebased biomolecules. For example, many excellent organometallic transformations have found applicability in glycoconjugate chemistry. Furthermore, the advance of physical organic chemistry has yielded a deeper understanding of the mechanism of glycosylation reactions, consequently allowing several new glycosylation approaches to be developed. These advances, coupled with those made in biology and biotechnology, have thus further solidified the necessity of effectively interweaving chemistry and biology. It is here, where chemistry and biology meet, that many more breakthroughs across various disciplines will undoubtedly be made.
6.01.2 Overview The 20 additional chapters that comprise this volume provide a detailed look at carbohydrates and their uses both in a laboratory setting and in nature, while also examining a variety of other important biomolecules and associated processes. The first three chapters, contributed by Peng George Wang, Ashraf Brik, and Zhongwu Guo, consider how carbohydrates can be utilized for synthetic purposes. Both enzymatic and chemical modes of synthesis are discussed with regard to their use for complex carbohydrate, glycoprotein, and vaccine production. Applications of mass spectrometry to analysis of glycans are then explored in the next two chapters as authors Kay-Hooi Khoo and Jianjun Li discuss some of the more advanced technologies in the field. Chapters 6.07–6.09 offer a look at the burgeoning field of chemical glycobiology. A broad look at this area is first presented by Jennifer Kohler in Chapter 6.07 with topics ranging from chemoenzymatic approaches to understanding glycan structure and function to the use of photocross-linkers for the covalent trapping of interactions between glycans. The final two chapters of this section, written by Alan Elbein and Howard Hang, take a more focused approach, considering how certain processes can be studied through the use of inhibitors and probes. The next section of this volume introduces how carbohydrates are utilized in a variety of biosynthetic pathways. Specifically, author Miguel Valvano first considers O-antigen biosynthesis, a process that is essential in the production of lipopolysaccharide. A discussion of the generation of glycoproteins in both mammalian and bacterial systems follows in the next two chapters with contributions from Inka Brockhousen and Mario Feldman. Subsequently, the structure and biosynthesis of the mycobacterial cell wall and glycosaminoglycans are examined by Dean Crick and Jian Liu in Chapters 6.13 and 6.14, respectively. The reader is then offered a section by Jack Preiss, which details the processes of bacterial and mammalian glycogen biosynthesis, while also examining the production of starch in plants. Finally, Rajai Atalla’s contribution, Chapter 6.16, focuses upon celluloses and their various roles in nature. In the closing chapters of this volume, a variety of other important biomolecules and related processes are highlighted. Specifically, Norman Lewis and Daneel Ferreira describe lignins and proanthocyanidins in Chapters 6.17 and 6.18, specifically looking at the chemistry and biology of these highly aromatic molecules. 1
2 Overview and Introduction
The final three chapters then direct attention to the areas of DNA and RNA with Darrell Davis first illustrating the importance and utility of nucleoside analogs. Chapter 6.20, written by George Garcia, subsequently examines how RNA is modified enzymatically and the corresponding consequences thereof before the structures and roles of riboswitches in regulatory processes are presented by Tina Henkin in Chapter 6.21. As is quite apparent, the topics that appear within this volume vary quite extensively. However, whether it is a discussion of the transfer of an oligosaccharyl moiety to a serine residue in O-glycosylation or the regulation of transcription termination through a riboswitch, it is hoped that the reader will not only come away with an appreciation for all of the biomolecules discussed, but more importantly recognize the diversity of processes that these small molecules and associated polymers can perform and/or regulate.
Biographical Sketches
Robert Woodward obtained a B.A. in chemistry (2006) and a B.S. in biology (2006) from The Ohio State University. He is an NIH Chemistry–Biology Interface Program Predoctoral Fellow currently pursuing a Ph.D. in organic chemistry at The Ohio State University. His research focuses on the applications of synthesis for studying complex biological processes such as polysaccharide biosynthesis and oligosaccharide transfer.
Peng George Wang obtained a B.S. in chemistry (1984) from Nankai University, China, and a Ph.D. in organic chemistry (1990) from the University of California, Berkeley. He then conducted postdoctoral research at the Scripps Research Institute before becoming an assistant professor in 1994 at the University of Miami in Coral Gables. From 1997 to 2003, he was a faculty member at Wayne State University. Since then, he has served in the Departments of Biochemistry and Chemistry at The Ohio State University as Ohio Eminent Scholar in Macromolecular Structure and Function.
Overview and Introduction 3
Research in the Wang laboratory is predominately focused on four areas of glycoscience. Glycochemistry: Work is centered on the generation of uncommon sugar libraries as well as the synthesis of key intermediates in carbohydrate-based biological processes, which are essential for their study. Glycobiology: Biochemical characterization of carbohydrate-active enzymes and investigations of the biological functions of carbohydrates in human diseases, immunity, and general microbiology are performed. Glycotechnology: Biosynthetic pathways are engineered for the synthesis of glycopharmaceuticals, polysaccharides for vaccine development, and biomedically important human glycoproteins. Glycoanalysis: Analysis of carbohydrate composition, sequence, structure, and their interaction with proteins through MS, NMR, QCM, and other analytical methods is conducted.