Databases of complex carbohydrates

17 M 49

Review

‘1

Databases of complex

II

carbohydrates J. Albert van Kuik and Johannes F.G. Vliegenthart

The cunm ~rwrv.u in complcx carhuhydmtc~ ’ r;lngc\ from \tudy,ng ths phy\ic;ll prupcn,c\ (II’ polysrchandct 10 clucid;:li,,g the mu,lwnlcnl of plycwon~ug~lc~ ln h,c,lopical rccogmlion. The lallrr fwlurv i\ exmrvmcly imponanc. \incc ,hc cnrhohydrex mo,c,,e\ (Ii glycoconjugates ruch aa glycopmreins and glycolip,dr pla) key role* I\ rca,gn,t,on de,cm,inanls m protem largcling and cell-ccl1 m,crxw,n~. and a\ cell-\urlacc rcccf~urs. The carbohydrate rnoictw* 01 plycopnwm~ arc dc~crnwwd hy the ongin and type (,I’ the cell m wh,ch II,C

pn,cc,n\ arc cxprcwd and. ,o wrw cxten,. hy Ihe wucWC 01 the pmtcin. For the hiotcchnological pmduction of rccomhirunl glycoprurcins ,n hewrologous cell lypc\. it i\ imponanr to undcr\land ,he influence Ihat wgar chain\ have on ,hc ch;lrilcteristic\ of lhcr cornpwnd~. The cnorn,ou\ ~~ructur;ll dwerwy of ol,govnccharidc\ ar,w\ t’ru,,, the w,dc vancry 01’ componcnl monoracchandc rc\,duc\. cwh 01’whtrh. in ,um. can have dil’furcn, a”,,,,,cr,l‘ ronl,purcl,on* .md ring lorm Thc*l~ rLwlUC\ NC wnnwtcd ,‘IJ m,rr-gl)corid,s I,nk;lpc\ al d,flcrcnl p,,\,~,,,n\, and can alw comilm non-carlwhydrare wh\t~,ucnt\. The primary \truc~rt‘~ of thouunds of “atur~lly tuwrmp cartwhydmtc ch.un\ (iwl;r,cd l’rom many dillerent wurcc~) have hcc,, rcponcd. together with mformution on thc,r hiolc>gical and/or phyvcol pr,,pev r,c, IC g. their ah,ll,y lo hind lu Iwtin* or TV,antihtdw. and cw,l’omla,,on.d da(d)

~Iruclurc~ 10 hc medc. raking , lo accounl Ihal i, ~wld hc cxlrcmely dilhcul, III huld 8 w114yIng vxch pntlilc from watch (Fig. ?) To cnler a cxbohydrate w~~turc Ihd, i\ a rchahlc surch prolilc for C&Bank rcqurc~ sxperiercc and a thorough understanding of the carhohydrate nomcnclaturc. Funhermorc. lypmg error\ arc easily made when a bmnchcd s~rw~ure i\ cmrred: Ihe I) or I conliguntton. Ihc anomeric conligum,ion. Ihc ring form and Ihc non-carhohydrale wh~,i,ucn,c mu\, he wrrcc~ and complc,c.

The residue-complex

concept

‘To make i, fwihlc lw tocxpcncnccd uvzr\ IO w.wh for hranchcd carhuhydraw \,ruc,urc\. CnrhB.mk u\,.\ the ‘rcsidur-wnplca’ concept. A residue-complex I\ J struclural clcmen, Iha, zompnw!~ J monowcchondc widuc together with all rc\iduc\ lhut arc allached LO II The pro~rarn wwchc\ for all carhohydmw \,ruc,urc\ Ihal c, %iin this rcvdue-complex elrmcn,. The uwr IX guided Ucp hy *lep m bwldmp 1hz residue-complex: for each rlep. Ihr uwr i\ prompted IO rhowc from a Ii\, 01 relevant items. which I> dcri\cd from all Jara m Ihc om only da&w. In ,hi\ way it warch p! ,I.‘- Is hail, ,ho\e ilems Iha, really ex~\l in the CCSD. The lir*r seleclion ha\ IO he made from il general clw of mww\xchande\ le.& Man). Nexr. LI cc~,uplc,u rcvduc ha\ IO he sclcctcd from a second Ii\1 (e.g. P-o-Monpl. t For carbohydrate nomenclarurc abbrcvia,ions. wc Flux 2.t SuhwquenIly. ,hi\ r&due ix cxlendcd tiith linkage\. from a llrl of IInkagc pa,lcm\ tc,g 1.3.linked). and linally a residue-complex can_ he ~clec,ed. such a\ a-o-Manp-

lind C!ICdcbircd ~.JCIUI~ i\ IO hrowc through it. hu, II the numlwr of ‘hi,\‘ t\ IOU Iargc. ~upplcmcntar) scurchc\ can he made Iha, narrow the numher of hunchc, or monosuzcharidc rcsiduc\. ot thd pu other cons,rain,\ cm the Ii*, hy wing diffcrcn, warch prolilcc. If a ~~ruucIure is wlcc:cd from the ht,li\,. 3 homology xwch can gwc all 1hc chations Iha, cordnin exactly tha, s~ruc,urc or \~rwIurc~ Iha, an: closely rclatcd. wch a\ \~rt~uc,"rcs Iha, have u~hcr nonsutwhydr~te wb~,i,uen,~. In a \irmlar way. gutded aearchcs can bc nude for olhcr wm*. huch a\ au,hor-’ nunc~. journal narncs. year of puhltcation. words in the title of an ankle. word\ in all IL‘XI Ii&h. molecular fomxdac and nominal molecular maw. CCSD records contain IWO other ca~cgorics of mfwmauon in addition IO lhc carhohydrotc structure and Ihc hlhhographicul data. The lir\, category \ummari/c\ uddttioncll detail\ Ihu, may hc prewnc in the wttclc. wch .ts attalyticul mc,htd\. binding of Ihc wrhohydrats chlcm IO lecrinr or antlbodics. Ihr pwitwn of at,achmcn, IO Ihc prowin. Ihc hiologicul wurcc and rhc hiolopicel ;Ic,i\i,y. The second category provtder link\ IO other daratiwz hy giving pawn, numben and accewon numhcr\ 1c.g IO CAS. the Intcmationnl f'rotem Sequence Datahaw IPIR) or the Prokin Data Bank (PDB)I.

An NMR spruiroscopy

database

The CCSD. as a daabasc of primary stmclurcc( cf cubobydrate chains. can he ..ud IO build other datahascs that permil awe\, to extra informalmn on there wuctutes. One &lx wnopice carhohydrale databaws including fast-atom bombs hnent gnaw cpectrometry (FABMS) or nxkar m~r.wc retoswce (NMR) spectmscopy data, or da1abaw cwdning threedimensional information obtaim! hr-01 X-m: crystallography. NMR-NOE (nuclear Ovcrharrwr effect) measurements or molecular dynamic\ &xlations. Indeed. a database rhac combines the WUCIURS of carbohydrates with NMR spctroscopic dam ha5 already been cons1rw1cd‘ (Elijvoet Center. Department of Bin-Organic Chemistry. Univenily of Umcht. NL-3584 CH Utrecht. The Netherlands). To determine the primary stroctwe of complex carhohydrate chains. tables of ‘H NMR and “C NMR chcmical shifts am used crlcnsively. These tables are uzuallg acquired from the literature” I’. Allhough review articles pmvide easy access to the da& they usually cover only a sclec~ed part of all the NMR data available. arc neilher corrected oar updated. and have to be surveyed manually. These am gomi reasons IO SIOR NMR tables in a computer database. and IO develop a program for easy mampulation of the daw. The datahasc tha1 has emerged uses a relational m&l IO ccmbine complex carbohydrate ~buc~rcs. bibliographic data. ‘H NMR tables and “C NMR tables. The carbohydrate srmcture~ and the

bihliugruphic dala air tlw pw2luminantly frum Ihe CCSD. whewas the NMR table> are collected fmm the literatuw. The darabaw-management program run\ on IBM-compatihlr perwnal computers under MS-DOS, and daraba\e and program together currently require 5 Mb of disk space. AI present the NMR da1a set coosists of 734 tables of ‘H NMR chemical shifts (Fig. 3). essentially corrcsportding 10 oligosaccharidcc derived from glycopmtcins. and 258 tables of “C NMR chemical ,hif1\. generally awxiatcd wilh ftagments of polyxxcharide*. To \earrh for 1he primary structure of a carbohydrate chain within 1hc NMR datahasc program. the construeIIO~ of a search profile i\ rcquircd. Tniz protilc conx;st\ of a lisl of chemical shift wlues and ao optional Ii-1 of monowxharidc residucc that can bc used to specify the ‘background‘ of the chemical shif1 values that pmduce a hit. The wuctures in the dalabauz are organized by carhohydmrc chain cy,c (e.g. N-linked. O-hnkcd or polyucchande: we Box 2) mlo dlffcrcnt section\. which can bc \carchcd wpam1ely. In addirion. the mmimum perccnrage of matchmg chemical shift values per s~ruc~urc thac will result in a hit and the tolerared vatialion of malching chemical shift values can be defmcd. AC:er a search. the hitlist of ~~n~c~ure and correhpondmg NMR tables arc simvltancously dicplayed. such thar 1hc matching monosaccharide rwdues in the s1ructums and lhe chemical \hif1 values in me tables arc highlighted. Thi\ prcscntalion clearly dcmonstratez which part of 1hc carbohydralc WUC~UR displayed is recognized by 1hc \cnrch protilc. and which chemical shift value\ arc inuc!\?d m 1his recognition. In this way. \earchc\ for known carhlhydratc stmclure~ can bc perIomlcd ca\ily. A novel ahpcc1 of the program. which 1s a major advantage. i\ 1hat it ciln alw a&t in dctcrmination of the ~trwturc of unknown curbnhydretc cham\ hy wggc\ting structural clcmcnt\ that may he pan of thevz unknown chain*. A\ the number of published rehles of NMR chemical shlfi values I\ growing exponcnlially. iti computerimd approach III NMR data storage an3 ~11c1~rc rcrneval i\ cwnlial. The gmwinc we of the NMR databacc mcvitahly IzuJ* III p&ng the dataha\r IO other platform\ (e.g. UNIX).

Future prospects for carbohydrate

databases

In the ruturc. we expert IO VY the creation of new carbohydrate databa\e\. wch a\ a databaw of thrcedlmcn.Gonal ~trucwrc~ of corhohydnw chains. All wch datahew together will provide 1hc carbohydrate chcmis1 wilh the necc\uy rools to keep up lo date with the growing amoun1 of wailuhlc mformatlon.

Acknowledgements Thl\ work ha\ hccn wppxted hy grants from the EC Biolcrhnology Acrwn Program BAP-03WNL. and by the EC Biotechnology Research for Innovarion. Dwelopnwnt and Growth in Europe (BRIDGE) BIOTCT90-0 184.

76

iwxh B~“,kw 5.3 I,. xi. 47;

References

Viewpoint

Talking straight: The sc~emd~ commumty. needs

IO

and e~peclally the tocd mduq.

make the efiolt IO communicate hone+

with conwmerr

and (Iearly

The benefits to industry of

about new product< and lethnlques ln order

IO avoid nwundenlandmg

and misreprercntatlnn.

Thr need

to develop such a communlc atmn and marketl,g rtratqy is an Important challenge fxmg the tmergmg tur,t~onal k~cds sector.

In this article I hhall concentrate wt ju\r on the benclils of communicating devclopmcm! in food scicrre and diet philosophy IO consumen. but aI*0 on consumer perceptions and lhc need for all communicwom 111 be open. honest and timely. In a f?\t-moving world. there I\ an ever-IncrcaGng need IO ;ommuniratc Ihe often complex and technical changes that are taking place ln as waightforward a manner as possible. To paraphrase Noribco~e Parkinwn. the vacuum created by a failure IO communicate will incviIablv he tilled with rumour and miweprcwntation. In Ioday’s informa!ion age, this need IO qxak plainly and openly is true for all industries. but is especially true for the food industry. JS WC are all consumers. II is clear that conwmcr perceptions play a large pan in UIC success of Ihe branding and marketing of any pmdua ‘What’s m a name‘ and how il is perceiled are vital IO that SUCCCSS. Those involved in irradiated foods know only 100 well the difticultw~ of overcoming the hurdle Ihal the wry mcmion of ‘that word’ cnx~cs for mos, comumer~. Irradiation has been used in food pre\crvaIion smce 1905. and while there are some rcwrvaIions among the scienlitic communily. lhc weigh1 of scientific opinion agree- Ihar II is wfe for JSC In the fotJ scc~or. The process has been awepIed by the World Hcalrh Organihalion since 1961. and yet how many conwmerr. given a choice. would buy a food labelled ‘irradiated’?

communicating advances in food science and diet philosophy Gerry Griffin llw hiolechnology induwy &o face\ an uphill Ia\k in removing the s&ma of such phrax\ as ‘genetic engineering‘. ‘growth hormones’. ‘genetically mod.!ied organisms and ‘gene Iechnology’. Consumers can rarccly he blamed for being appw hcnbive ahout new technologies and ‘new foods’ when wmc of the Ierminology is Ias than coowmcr friendly. Add IO that the food SCM\ of lhc past couple 01 yem and you can see how it has become a uusm that most people are oat worried nbou~ anything - ,%Y than the food they cat. rhe water they drink. ~hr mr they breathe. Ihe land they llve on and 1he energy they “SC Three yrm ago. the opening of the can of worms of hod scares - wirh iI\ focus on what wan gwd or bad and tlx riw of conflicling adwce from induwy cxperlz and activist group\ - led ccnwmen IO become sceplical and apprehcnrivc. if no1 cynical about how Ihcir food was pruduccd. Unfonunately. Ihe legacy oi this period i\ lhal rome con.wrws. and preswrc group\ have a tendency IO dwell on the risks and pmblcms of the technology of food produccmn r&a than on the opporIuniIie\ afforded hy new development\.