Download Advances in carbohydrate chemistry and biochemistry 1st edition derek horton (eds.) ebook A

Page 1


AdvancesinCarbohydrateChemistryand Biochemistry1stEditionDerekHorton(Eds.)

https://ebookname.com/product/advances-in-carbohydratechemistry-and-biochemistry-1st-edition-derek-horton-eds/

Advances in Carbohydrate Chemistry and Biochemistry 1st Edition Derek Horton (Eds.)

https://ebookname.com/product/advances-in-carbohydrate-chemistry-andbiochemistry-1st-edition-derek-horton-eds/

ebookname.com

Hydrolysis in Drug and Prodrug Metabolism Chemistry Biochemistry and Enzymology 1st Edition Bernard Testa

https://ebookname.com/product/hydrolysis-in-drug-and-prodrugmetabolism-chemistry-biochemistry-and-enzymology-1st-edition-bernardtesta/

ebookname.com

Advances in Child Development and Behavior 29 1st Edition Robert V. Kail And Hayne W. Reese (Eds.)

https://ebookname.com/product/advances-in-child-development-andbehavior-29-1st-edition-robert-v-kail-and-hayne-w-reese-eds/

ebookname.com

The Colour of Injustice The Mysterious Murder of the Daughter of a High Court Judge 1st

Edition John Hostettler

https://ebookname.com/product/the-colour-of-injustice-the-mysteriousmurder-of-the-daughter-of-a-high-court-judge-1st-edition-johnhostettler/

ebookname.com

Ecology for Nonecologists 1st Edition Frank R. Spellman

https://ebookname.com/product/ecology-for-nonecologists-1st-editionfrank-r-spellman/

ebookname.com

LMF Lexical Markup Framework 1st Edition Gil Francopoulo

https://ebookname.com/product/lmf-lexical-markup-framework-1stedition-gil-francopoulo/

ebookname.com

The Art of Grammar A Practical Guide First Edition. Edition Alexandra Y. Aikhenvald

https://ebookname.com/product/the-art-of-grammar-a-practical-guidefirst-edition-edition-alexandra-y-aikhenvald/

ebookname.com

Multidimensional Evidence Based Practice Synthesizing Knowledge Research and Values Social Work Practice in Action 1st Edition Marvin D Feit

https://ebookname.com/product/multidimensional-evidence-basedpractice-synthesizing-knowledge-research-and-values-social-workpractice-in-action-1st-edition-marvin-d-feit/

ebookname.com

Louis Agassiz as a Teacher Illustrative Extracts on His Method of Instruction Lane Cooper

https://ebookname.com/product/louis-agassiz-as-a-teacher-illustrativeextracts-on-his-method-of-instruction-lane-cooper/

ebookname.com

Early childhood mathematics 2. ed Edition Sperry Smith

https://ebookname.com/product/early-childhood-mathematics-2-ededition-sperry-smith/

ebookname.com

AcademicPressisanimprintofElsevier

Radarweg29,POBOX211,1000AEAmsterdam,TheNetherlands LinacreHouse,JordanHill,OxfordOX28DP,UK

32JamestownRoad,LondonNW17BY,UK

30CorporateDrive,Suite400,Burlington,MA01803,USA

525BStreet,Suite1900,SanDiego,CA92101-4495,USA

Firstedition2010

Copyright # 2010ElsevierInc.Allrightsreserved

Nopartofthispublicationmaybereproduced,storedinaretrievalsystemortransmittedinanyform orbyanymeanselectronic,mechanical,photocopying,recordingorotherwisewithouttheprior writtenpermissionofthepublisher

PermissionsmaybesoughtdirectlyfromElsevier’sScience&TechnologyRights DepartmentinOxford,UK:phone(+44)(0)1865843830;fax(+44)(0)1865853333; email: permissions@elsevier.com.Alternativelyyoucansubmityourrequestonlineby visitingtheElsevierwebsiteat http://elsevier.com/locate/permissions,andselecting ObtainingpermissiontouseElseviermaterial

Notice

Noresponsibilityisassumedbythepublisherforanyinjuryand/ordamagetopersonsorpropertyas amatterofproductsliability,negligenceorotherwise,orfromanyuseoroperationofanymethods, products,instructionsorideascontainedinthematerialherein.Becauseofrapidadvancesinthe medicalsciences,inparticular,independentverificationofdiagnosesanddrugdosagesshouldbemade

ISBN:978-0-12-380856-1

ISSN:0065-2318

BritishLibraryCataloguinginPublicationData

AcataloguerecordforthisbookisavailablefromtheBritishLibrary

LibraryofCongressCataloging-in-PublicationData

AcatalogrecordforthisbookisavailablefromtheLibraryofCongress

ForinformationonallAcademicPresspublications visitourwebsiteat books.elsevierdirect.com

1011121310987654321

LISTOFCONTRIBUTORS

C.FredBrewer, DepartmentofMolecularPharmacology,Microbiologyand Immunology,AlbertEinsteinCollegeofMedicine,Bronx,NewYork,10461,USA

KlausBuchholz, DepartmentofTechnicalChemistry,TechnicalUniversity, Braunschweig,D-38106,Germany

YoannM.Chabre, DepartmentofChemistry,Universite ´ duQue ´ beca ` Montre ´ al, Montre ´ al,Que ´ bec,H3C3P8,Canada

TarunK.Dam, DepartmentofMolecularPharmacology,AlbertEinsteinCollegeof Medicine,Bronx,NewYork,10461,USA

R.ColinHughes, NationalInstituteforMedicalResearch,MillHill,London,UK

LennartKenne, DepartmentofChemistry,SwedishUniversityofAgricultural Sciences,Uppsala,Sweden

OlleLarm, ExTheraAB,KarolinskaSciencePark,Stockholm,Sweden

AlfLindberg, DepartmentofClinicalBacteriology,KarolinskaInstitutet,Huddinge UniversityHospital,Huddinge,Sweden

SusanaD.Lucas, CentrodeQuı´micaeBioquı´mica/DepartamentodeQuı´mica eBioquı´mica,FaculdadedeCie ˆ nciasdaUniversidadedeLisboa,Ed.C8,5○ Piso, CampoGrande,1749-016,Lisboa,Portugal

Ame ´ liaP.Rauter, CentrodeQuı´micaeBioquı´mica/DepartamentodeQuı´mica eBioquı´mica,FaculdadedeCie ˆ nciasdaUniversidadedeLisboa,Ed.C8,5○ Piso, CampoGrande,1749-016,Lisboa,Portugal

Rene ´ Roy, DepartmentofChemistry,Universite ´ duQue ´ beca ` Montre ´ al,Montre ´ al, Que ´ bec,H3C3P8,Canada

MiguelSantos, CentrodeQuı´micaeBioquı´mica/DepartamentodeQuı´micae Bioquı´mica,FaculdadedeCie ˆ nciasdaUniversidadedeLisboa,Ed.C8,5○ Piso, CampoGrande,1749-016,Lisboa,Portugal

x LISTOFCONTRIBUTORS

Ju ¨ rgenSeibel, InstituteofOrganicChemistry,UniversityofWurzburg,AmHubland, D-97074,Wu ¨ rzburg,Germany

NathanSharon, WeizmannInstituteofScience,BiologicalChemistryDepartment, Rehovot,Israel

NunoM.Xavier, CentrodeQuı´micaeBioquı´mica/DepartamentodeQuı´micaeBioquı´mica,FaculdadedeCie ˆ nciasdaUniversidadedeLisboa,Ed.C8,5○ Piso,Campo Grande,1749-016,Lisboa,Portugal

PREFACE

Synthesishasbeenasustainedareaofmajorinterestincarbohydratescience,andthe precedingVolume62ofthisseriesfeaturedthreechaptersfocusingindetailonthe constructionofglycosidiclinkages.Manyestablishedsyntheticmethodspermitthe elaborationofcomplextargetmolecules,butfrequentlyinvolvetheuseoftedious protection–deprotectionsequencesandexpensiveorhazardousreagents.Thiscurrent Volume63of Advances presentstwoarticlesthatofferpromiseofusefulmethodologiesforsimplifiedproceduresamenabletolow-costlarge-scaleapplications,using mildconditionsandenvironmentallyfriendlymaterials.

RauterandhercoauthorsXavier,Lucas,andSantos(Lisbon)presentherea detailedoverviewofthepotentialforheterogeneouscatalystsinusefulsynthetic transformationsofcarbohydrates.Suchsilicon-basedcatalystsaszeolitesareeasy tohandleandrecover,arenontoxic,andcanofferinterestingpossibilitiesforexercisingstereo-andregio-controlinmanyestablishedcarbohydratetransformations.

Inthemidstofwide-rangingresearchontheroleofcomplexoligosaccharidesin biologicalrecognitionprocesses,andtheattendantfocusonsynthesisofsuchmolecules,theimportantroleofoligosaccharidesinlarge-scalecommercialapplicationsis oftenoverlooked.ThecontributionbySeibelandBuchholz(WurzburgandBraunschweig)inthisvolumeaddressesindetailthosetoolsofparticularvalueforpreparation ofoligosaccharidesthatserveneedsinthefood,pharmaceutical,andcosmetic industries.Majoremphasisisdevotedtotheuseofreadilyavailableenzymes(glycosidases,glycosynthases,glucansucrases,fructansucrases)andabundantcarbohydratesubstrates,especiallysucrose,andtheapplicationsofenzymeandsubstrate engineering.Particularattentionisgiventothoselarge-scaleapplicationsofoligosaccharidesthatserveassweeteners,aswellaspromisingnewmedicalapplications.

Twocomplementarytreatmentsdealwithdifferentaspectsoftheintensecurrent interestinthebiologicalrecognitionphenomenabetweencarbohydratesandproteins. DamandBrewer(NewYork)examineindetailtheenergeticsandmechanismsof bindingbetweenlectins(carbohydrate-bindingproteins)andthemultivalentglycoproteinreceptorsonthesurfaceofnormalandtransformedcells,aswellasothertypes ofcarbohydratereceptors,includinglinearglycoproteins(mucins).Theauthors postulateacommon‘‘bind-and-jump’’mechanismthatinvolvesenhancedentropic effectswhichfacilitatebindingandsubsequentcomplexformation.

Inanextensiveandcomprehensivesurvey,ChabreandRoy(Montreal)revisitthe subjectofneoglycoconjugatesintroducedthreedecadesagobyStowellandLeein Volume37ofthisSeries.Itwasthenanascenttopic,andtheMontrealauthorsnow bringtogetherinasinglelargearticlethevastnewliteraturebasethathas

subsequentlyevolvedinthefieldofthe‘‘glycosideclustereffect.’’Theyearshave witnessedmuchcreativityinthedesignandstrategiesofsynthesisthathaveafforded awidearrayofnovelcarbohydratestructures,andreflecttheongoingdynamic activityinthisrapidlyevolvingarea,evensincetherecentarticlebytheNicotra groupinVolume61ofthisseries.Elaboratenanostructures,nowtermedglycoclusters andglycodendrimers,featurearraysofcarbohydrateepitopesjoinedvialigandsonto avarietyofscaffolds,includingcalixarenes,porphyrins,andsuchcarbonnanostructuresasfullerenesandnanotubes.Theirsynthesisandcharacterizationisaddressedin detailalongwithevaluationviasuchtechniquesasmicroarraysandothermodern analyticaltechniques,fortheirpotentialinapplicationtobiologicalsystems.

Thecontributionsoftwooftheworld’sleadingcarbohydrateinnovatorsarerecognizedinthisissue.TheworkofRogerJeanlozevolvedfromaclassicalbackgroundin synthesisandstructureelucidationtowideapplicationsinthebiologicalareawhich haveledhimtobeconsideredasthefatherofthesubjectnowknownasglycobiology. Hecontributedextensivelytothese Advances,witharticlesinVolumes6,11,13,and43 oftheseries,andhislifeandscientificworkisthesubjectoftheobituaryarticleby Sharon(Israel)andHughes(London).ThearticlebyKenne,Larm,andAlfLindberg (Stockholm)surveysthecareerofBengtLindberg,andespeciallynotesLindberg’s developmentofthemethodologyformicroscaleanalysisofcarbohydratestructuresthat haspermitteddeterminationofthesequencestructureofminutesamplesofoligo-and poly-saccharidesfrombiologicalsourcesandhasenabledtheexplosivegrowthof modernresearchinglycobiology.Lindbergwasalsoanotablecontributortothisseries, witharticlesinVolumes15,31,33,and48thatdocumentinLindberg’sclassicterse styletheevolutionofstructuralmethodologyfromearlybeginningstosophisticated applications,inparticularforbacterialpolysaccharides.

ThedeathonOctober8,2009ofAntonioGo ´ mezSa ´ nchezisnotedwithregret.He wasoneofthesuccessorsoftheSevillecarbohydrateschoolbuiltupbyFrancisco Garcı´aGonza ´ lez,withwhomhecoauthoredinVolume20achapteronthereactionof aminosugarswith1,3-dicarbonylcompounds,asubjectthatwasamajorthemeof Go ´ mezSa ´ nchez’sresearch.

SincerethanksareexpressedtoProfessorsStephenAngyalandJ.GrantBuchanan fortheirmanyyearsofadviceandsupportasmembersoftheBoardofAdvisors. WelcomedasanewmemberoftheBoardisProfessorToddLowary.

Washington,DC November,2009

ROGERW.JEANLOZ

1917–2007

RogerWilliamJeanloz,whopassedawayonSeptember12,2007,6weeksshortof his90thbirthday,wasamongtheearliestpioneersinthefieldnowknownas Glycobiology.Hemadeseminalcontributionstothesubject,andtrainedanumber ofleadersinthefield.Hewasoneoftheprimeorganizersinthe1950softhe Glycosaminoglycan,Glycoprotein,andGlycolipidGroup(knownasthe4Gs), laternamedtheSocietyofComplexCarbohydrates,andeventuallytheSocietyfor Glycobiology,ofwhichheservedasPresidentin1974.

FromGlycogenandDeoxySugarstoComplexCarbohydrates

JeanlozwasbornonNovember3,1917inBerne,Switzerland,toaFrenchmother andaSwiss–Germanfather.HewasbroughtupinFrench-speakingGenevawherehe pursuedclassicalstudiesemphasizingGreekandLatinatCollegeCalvin.In1936,he wasawardedtheB.S.degreefromthisCollegeandin1941aDiplomainChemical EngineeringfromtheUniversityofGeneva,wherehestudiedorganicchemistryand biochemistry.Hiskeeninterestinscienceandresearchbeganin1941whenKurtH. Meyer,wellknownforhispioneeringstudiesoncelluloseandstarch,acceptedhimas adoctoralstudent.InMeyer’slaboratory,Jeanlozinvestigatedtheenzymaticdegradationofstarch1 andthenthestructureofmuscleglycogen.2 Thelatterstudieswere thesubjectofhisD.Sc.thesis,completedin1943.Atthesametimeheservedashead instructorfororganicchemistry.

In1943,afterbeingawardedtheD.Sc.degree,JeanlozwasappointedasResearch Associate,firstwithMeyerandthenwithTadeuszReichstein,NobelLaureateforhis workonsteroidhormones.WithReichsteinhestudiedthechemistryofdeoxysugars, someofwhichareconstituentsofthesehormones,anddeveloped3 anewmethodfor theassayofthesesugars.In1946–1947hespent1yearinCanadaasResearch AssociateattheUniversityofMontreal,wherehecollaboratedwithD.A.Prins fromtheResearchDivision,ClevelandClinic,Cleveland,OH,inthepreparationof

ISBN:978-0-12-380856-1

DOI:10.1016/S0065-2318(10)63001-6.

4

NATHANSHARONANDR.COLINHUGHES

areviewofthechemistryofcarbohydrates4 fortheprestigious AnnualReviewsof Biochemistry,thefirstofmanyimportantoneshewroteduringhisscientificcareer. HethenmovedtotheUnitedStates,whereheworkedfor1yearasaSeniorResearch FellowintheNationalInstitutesofHealthlaboratoryofthenotedcarbohydrate chemist,ClaudeS.Hudson,wherehebecameinvolvedinthestudyofriboseandits derivatives5–7,andhecontributedwithHewittFletcherfromthesamelaboratorya review8 onthechemistryofriboseinthefledgling AdvancesinCarbohydrate Chemistry.Thefollowing3yearswerespentattheWorcesterFoundationfor ExperimentalBiology,thenunderthedirectionofthenotedendocrinologistGregory Pincus,workingonsteroidhormones,asubjectonwhichhecontinuedtocollaborate withthePincusgroupforseveralyearsthereafter.9–14

In1951,JeanlozwasinvitedbyDr.WalterBauer,ChiefoftheMedicalServices andoftheArthritisUnitattheMassachusettsGeneralHospital,tobecomeamember oftheRobertW.LovettMemorialGroupfortheStudyofCripplingDiseases,andto organizealaboratoryforthestudyofthechemicalstructureofthepolysaccharidesof connectivetissueandofrelatedbiochemicalproblems.Tenyearslater,hewas appointedastheHeadofthenewlyformedLaboratoryforCarbohydrateResearch oftheLovettGroup,andin1969asProfessorofBiologicalChemistryandMolecular PharmacologyatHarvardMedicalSchool.Heheldthesepositionsuntilhisretirement,andcontinuedtobeactiveinresearchandteachingthereafter.Itwasinthe CarbohydrateResearchlaboratorythatJeanloz,duringhalfacentury,mademajor contributionstoourknowledgeofthestructure,biosynthesis,andfunctionofcomplex carbohydrates,anareathatnowfallsunderthesubjectofglycobiology.Indeed,he maybeconsideredasoneoftheearlyglycobiologists.

Mostprominentamonghiscontributionsweretheelucidationofglycosaminoglycan structures,chieflybymethylationanalysis;thesynthesisofrareaminosugars;establishmentofthestructureofthepolysaccharidebackboneofthebacterialcell-wallpeptidoglycan;providingthefoundationforstructuralstudiesofthecarbohydratemoietiesof N-andO-linkedglycoproteins;synthesisofmanyoftheglycopeptideconstituentsof glycoproteins;detailedstructuralanalysisaswellassynthesisofseveralofthedolichyl sugarphosphatesinvolvedinproteinglycosylation;characterizationofglycansaccumulatedinlysosomalstoragediseases,andtheactionpatternofcatabolicglycosidases. Inaddition,analysisofTA-3glycoproteininitiatedinhislaboratoryledtothemost detailedinvestigationofanytumor-relatedglycoproteinexaminedatthetime.Hiswork hashadimplicationsinmanyareasofbiology,amongthembiochemistryandbacteriology,immunology,andcancerresearch.Adominantfeatureofmuchofthethisworkwas Jeanloz’semphasisontheimportanceofchemicalsynthesisofcomponentpartsof complexglycoconjugatesinordertodistinguish,forexample, D or L enantiomers,ring

structuresand a or b anomers,intheoverallstructureofbiologicallyactive macromolecules.

ApplicationsofMethylationAnalysis

BeforejoiningtheLovettGroup,Jeanlozdevotedconsiderableefforttounderstandingtheperiodateoxidationreaction,startingwithanexaminationofitseffects onglucosamine.15 HeandEnricoForchiellithenusedittoexaminethestructureof hyaluronicacid15,16 andchitin.17 Itrapidlybecameevidenttohimthatthismethod,as wasthecaseinthesuccessfuldeterminationofthestructureofsimplerpolysaccharidessuchasglycogenorstarch,requiredsupplementationwithotherones,particularlythemethylationtechnique.Thelattertechniquehadalreadybeenattemptedin thefieldofglycosaminoglycans,butwithoutpositiveresults.Themaindifficulty residedinthefactthatdegradationofamethylatedheteropolysaccharide,madeupof repeatingunitsofhexosamineanduronicacidwithdifferentlinkages,couldgiverise toalargenumberofmono-di-andtri-O-methylatedmonosaccharides.Itwas thereforenecessarytosynthesizeallofthereferencesubstances,andtoseparate andidentifytheminartificialmixtures.Jeanlozwasencouragedinthislongand arduoustask,whichrequiredgramquantitiesofstartingmaterials,bytheknowledge thatifshowntobeefficient,themethodcouldbeappliednotonlytotheelucidationof thestructureoftheglycosaminoglycansbutalsotootherclassesofcomplex carbohydrates.

Inthecourseofthe1950sJeanlozsynthesized13methylatedderivativesof glucosamineandgalactosamine(reviewedin Ref.18).Theseincludedthe4-methyl19 and6-methyl20 ethersofglucosaminehydrochlorideandthe3,6-and4,6-dimethyl ethersofthishexosamine.21 Concurrentlythe3-22 4-,23 and6-24 monomethylethersof galactosaminehydrochloride,andits3,6-25 and4,6-26 dimethyletherswerealso prepared.Methylatedderivativesofothermonosaccharideswerealsosynthesized subsequently,amongthemthoseofmuramicacid,withHaroldFlowers27 and N-acetylmannosaminewithNasir-ud-Din.28

Themethylatedglucosamineandgalactosaminederivativesinparticularwerein suchdemandbyotherlaboratoriesasreferencecompoundsthatoneresearchassistant workedfulltimesolelytoreplenishsuppliesofthesecompounds.Inthissynthetic approach,whichtook10yearstoaccomplish,Jeanlozwashelpedbyseveralassociates,includinghiswifeDorothy,andPierreJ.Stoffynwhojoinedhisgroupin1953 andstayeduntil1961.Oneofthemanyresultsoftheirproductivecollaborationwas theStoffynandJeanlozmethod29 foridentificationofhexosaminesbyninhydrin degradationtothecorrespondingpentoses,whichisstillthesimplestmethodto distinguishbetweenglucosamineandgalactosamine.

NATHANSHARONANDR.COLINHUGHES

ConnectiveTissueGlycosaminoglycanStructure

ThemethylatedderivativesservedasthebasisofelegantstudiesinwhichJeanloz andhiscolleaguesunequivocallyestablishedthestructureofhyaluronan,dermatan sulfate,andthechondroitinsulfates.Theyalsoclarifiedmanyconfusingissues, includingthepositionofthesulfategroupsinthesepolymers.Inthecourseofthis work,theyprovedthatdermatansulfatecontained L-iduronicacid,asugarnotknown beforetooccurinnature.

Applicationofthemethylationtechniquetohyaluronanestablishedthelinkageat position3oftheglucosamineI moietyandthelinkageatposition4oftheglucuronic acidmoiety.30 Eventually,hyalobiouronicacid[b-GlcA-(1 ! 3)-GlcNAc],therepeatingunitofhyaluronanwassynthesized;itwasidenticalwithoneoftheaciddegradationproductsoftheparentpolysaccharide.31,32 Jeanlozandhiscolleaguesalso isolatedmethylderivativesofhyalobiouronicacidfromthemethylated polysaccharide.

MethylationanalysisofchondroitinsulfateAshowedthatthesulfateislocatedat position4ofthegalactosaminemoiety,thatthe N-acetyl-b-galactosamineresidueis locatedatposition4oftheglucuronicacidmoiety,andthatgalactosaminepossessesa pyranosestructure.Thismethodgavealsoadditionalevidencefora b-(1 ! 3)interglycosidiclinkagebetweenglucuronicacidand N-acetylgalactosamineresidues, consistentwitharepeatingdisaccharideunitof b-glucuronate-(1 ! 3)-4-sulfo-Nacetyl-b-galactosamine-(1 ! 4).Usingthesametechnique,Jeanlozalsoinvestigated thestructureofchondroitinsulfateC,andprovidedevidencethatchondroitinsulfate Cisanunbranchedpolysaccharidecomposedofalternateresiduesofglucuronicacid and N-acetylgalactosamine6-sulfateresidues b-glycosidicallylinkedatpositions (1 ! 3)and(1 ! 4),respectively(see Ref.33 forareview).

Dermatansulfate,alsotermedchondroitinsulfateB,arelatedglycosaminoglycan constituentofconnectivetissue,wasknowntobecomposedofgalactosamineanda uronicacid,originallybelievedtobeglucuronicacidbutthenclaimedtobeiduronic acidbasedlargelyoncolorreactionsandpaperchromatography.However,the D or L-enantiomerstatusofthelattermonosaccharidewasnotclear.JeanlozandStoffyn unequivocallycharacterizedthemonosaccharideas L-iduronicacidbyconsecutive desulfation,reduction,andhydrolysisofthepolysaccharide,followedbyisolationof thecrystalline2,3,4-tri-O-acetyl-1,6-anhydro-b-L-idopyranose,whichwasshownto beidenticaltoanauthenticspecimensynthesizedfrom1,2-O-isopropylidene-b-Lidofuranose.34

IAllsugarsareofthe D configuration,unlessotherwisenoted.

Duringthiscarefulanalyticalworkonchondroitinanddermatansulfates,Jeanloz notedthatthestoichiometryofthepurifiedglycosaminoglycansindicatedsignificant heterogeneity,inparticularvariablesulfation.Itisnowknownthatsuchvariabilityin sulfationanduronicacidcontentsignificantlyimpactsontheabilityofconnectivetissuepolysaccharidestobindadiverserangeofbiologicallyactivemolecules, includinggrowthfactorsandproteaseinhibitors.

MammalianMembraneGlycolipids

Asearlyas1955,Jeanlozfeltthatthemethodsdevisedforthestudyofconnectivetissueglycosaminoglycanscouldbeappliedtootherclassesofglycoconjugates. TogetherwithSen-itiroHakomori,whocametotheLaboratoryforCarbohydrate ResearchfromtheUniversityofSendaiinJapan,heundertooktheoneroustaskof purifyingthesubstancesconferringhumanerythrocyteblood-typespecificity.ExtractionoferythrocytesofhumanAandBbloodtypeaffordedsmallamountsof glycolipids( 1mg/lofblood)possessingblood-groupactivity.Purificationwas obtainedbyadsorptiononactivatedaluminaandactivatedsilicagel,followedby partitionchromatographyoncellulose.Theactivesubstancesisolatedfromthetwo differentbloodtypesshowedgreatsimilarities.Partialhydrolysisshowedaresistant corecomposedoffattyacid,sphingosine,glucose,andgalactoseforthesubstances isolatedfrombothbloodtypes.Inbothsubstances,additionalresiduesofeither galactoseorgalactosamineconstituentswerelocatedat,ornear,theextremitiesof thecarbohydratechain,hintingatthepossibilitythatthesesugarswerepartofthe bloodtypeimmunodeterminants.35 Subsequently,theyisolatedfromhumancancerous tissueaglycolipidrichinfucose,36 andtogetherwithJerzyKoscielakandK.J.Bloch showedthatthisglycolipidcross-reactedimmunologicallywithhumanblood-group substances.37 Inaddition,thefirstdefinitiveevidenceoftheimmunogenicityof glycolipidswasobtainedbyimmunizingrabbitswithapurifiedglycolipid(globoside) withtheformationofaprecipitatingantiglobosideantibody.38 Theantibodyagglutinatedandhemolyzedhumanredcells,providedthattheywerepretreatedwithtrypsin.

BacterialCell-WallPeptidoglycan

Intheearly1960sJeanlozbecameintriguedbypeptidoglycan,therigidconstituent ofbacterialcellwallsthatendowsthesemicroorganismswiththeircharacteristic shape,whetherround(cocci)orelongated(bacilli).Atthetimeitwasbelievedthat thepolysaccharidebackboneofpeptidoglycanconsistsofarepeatingdisaccharidein which N-acetylglucosamineis b-(1 ! 6)linkedtomuramicacid(3-O-D-lactyl-Nacetylglucosamine),andthatlinkagebetweenthedisaccharideunitsinthebackbone is b-(1 ! 4).Toestablishunequivocallythestructureofthedisaccharide,the

8 NATHANSHARONANDR.COLINHUGHES

synthesisofmuramicacidanditsvariousderivatives,includingthedisaccharide bGlcNAc-(1 ! 6)-MurNAcwasperformedintheJeanlozlabbyHaroldFlowers39–41 andbyToshiakiOsawa.42 Theseincludedvariousmethylethers43 andglycosides,44 andacetylderivatives45 ofmuramicacidandits galacto46 and manno47 analogues, inthesynthesisofseveralofwhichPierreSinay ¨ wasinvolved.Additionally,muramic acid6-phosphatewassynthesized48 andtheabsoluteconfigurationofthecarboxyethyl(lactyl)side-chainofmuramicacidwasestablished.49 Inthecourseofthese studies,thepeptidoglycanpolysaccharidebackbonewasshowntocontainsome disaccharideunitshavingthe manno (ratherthan gluco)analogofmuramicacid.50 Methodsweredevelopedquiteearlyonforthelarge-scalepreparationofbacterialcell wallsfrom Micrococcuslysodeikticus (laterrenamed M.luteus)51 andfortheisolation ofthenaturaldisaccharidefromlysozymedigestsofthewalls.Comparisonofthe syntheticdisaccharidewiththenaturalonerevealedquitesurprisinglythatthetwo werenotidentical.Theconclusionwasthatthenaturaldisaccharideis b-(1 ! 4)linked,asisthepolysaccharidebackbonethroughout.52 Thiswasconfirmedby comparisonofthenaturaldisaccharidewithsynthetic b-GlcNAc-(1 ! 4)-MurNAc. Thebacterialpolysaccharideisthereforechemicallyhomologoustochitin.

Oneoftheminorbyproductsoftheisolationprocedureofthedisaccharidefrom lysozymedigestsofbacterialcellwallswasthetetrasaccharide b-GlcNAc-(1!4)b-MurNAc-(1!4)-b-GlcNAc-(1!4)-MurNAc.Thisstructureisreadilycleavedby lysozyme,andhasprovedtobeextremelyusefulinotherlaboratoriesforthestudyof themechanismofactionoftheenzyme.

InvertebrateMatrixGlycoconjugates

Inthelate1960s,Jeanlozbegananextendedstudyoftheextracellularmatrixof invertebrates.Earlier,Jeanloz’scolleagueintheLovettUnit,JerryGross,hadpointed outthatinvertebratematricescontainedgreaterandmorevariedamountsofcarbohydratethanvertebratematrices.TheJeanlozlaboratory,inparticularRichardKatzman, togetherwithAndyKangoftheGrosslaboratory,setouttoidentifythesepoorly characterizedglycoconjugatesfromthreeinvertebratephyla,theseaanemone Metridiumdiocanthus,theseacucumber Thyonebriareus,andamarinesponge Hippospongiagossypina 53–55 Themajoroligosaccharidechainoftheinvertebratecollagens, presentinhigheramountsthaninvertebratecollagens,wasshowntobe a-glucopyranosyl-(1 ! 2)-b-galactopyranosyl-(1 ! 5)-L-lysine,similartothemajorglycanof vertebratecollagen.Asparagine-linked N-glycanscontainingglucosamine,fucose, andmannosewerealsopresent.Furtherstudiesshowedthepresenceinseacucumber matrixoftwomajoracidicglycosaminoglycans,namelyachondroitinsulfatesimilar instructuretovertebratechondroitins,andanovelpolyfucosesulfate.Thislatter

componentwasnamedthyonatanandcharacterizedasan a-(1 ! 2)-linkedpolyfucose-4-sulfatepolysaccharide.Theabsenceofanaminosugardistinguishesthyonatan fromallknownvertebrateconnective-tissueglycoconjugates.Chondroitinandthyonatanwerenotfoundinspongesandseaanemone,leadingtothespeculationthat acidicglycoconjugatesplaynocrucialroleincollagenfibrilformation,contrasting withtheprevailingideaatthetimethatregularlyspacedacidicgroupsmayactasa templateuponwhichcollagenfibrilsarebuiltup.Interestingly,arabinosewasisolated fromspongeconnectivetissue:itsidentitywasconfirmedbythepreparationofa crystallinederivativeofbenzyl-1-phenylhydrazine.56 Althougharabinoseisacommonsugarinplants,itisveryrareinanimals.Katzmanproposedthatthearabinofuranosylnucleosidesofuracilandthymidine,isolatedinthe1950sfromsponges,may serveinbiosynthesisofarabinose-containingpolysaccharidesintheseorganisms. Interestininvertebratematrixglycoconjugateshasrecentlyincreased.Someofthese matrices,forexampletheseacucumber,haveanabilitytoaltertheirstiffnessin responsetochangesinpHorionicconcentrations,creatingthepossibilityofderiving newdynamicneocompositesforbiomedicalapplications.

RareAminoSugars

ThesyntheticstudiesofJeanlozledtothesolutionofmanyotherquestionsin carbohydratechemistry,especiallythatofuncommonaminosugars.Resultingfrom thesestudieswasthesynthesis,mainlywithDorothyJeanlozandwithSoniaTarasiejskayaofseveralaminosugars,someofwhichforinstance,gulosamine,57,58 had beenshowntobeconstituentsofaminoglycosideantibiotics,suchasthestreptothricins,andothersthatatthetimewerenotknowntooccurinNature.Theseincluded allosamineandtalosamine,3-amino-3-deoxyidose,and3-amino-3-deoxygulose,as wellas2,4-diamino-2,4-dideoxyglucose.59–61 Bacillosamine(2,4-diamino-2,4,6-trideoxyglucose),anotherrareaminosugar,wasfirstisolatedintheJeanlozlaboratory byNathanSharonfromabacterialpolysaccharidethathepreparedattheWeizman Institute,Rehovot.62 Thisstructure,determinedlaterelsewhere,hasrecentlybeen identifiedasaconstituentofthecarbohydrate–peptidelinkinggroupofglycoproteins ofmanyeubacterialpathogens,andappearstoberequiredfortheirvirulence.Itis thereforeattractingconsiderablecurrentinterest.

StructuralAnalysisofProtein-BoundOligosaccharides

Anumberofthecentralthemesofcurrentglycoconjugateresearchcanbetraced backtostudiesbegunintheJeanlozlaboratory.Oneprominentexampleisthe elucidationofthesequencesofthecarbohydrateslinked N-or O-glycosylicallyto asparagineorserine/threonineresiduesrespectivelyinglycoproteins.Littlewas

10

NATHANSHARONANDR.COLINHUGHES

knownaboutthesestructuresatthetime:rapidmethodshavesubsequentlybeen developed,providinginformationthatiscrucialinglycomics,describingthevariety ofglycanstructuresindifferentorganismsandtissues.Workwasinitiatedinthelate 1950sbytheJeanlozlaboratoryontwoserumglycoproteins,alpha1-acidglycoproteinandfetuinbyEdEylarandRobertSpiro,respectively.63–66 Inthiswork,purified glycosidases,suchas Diplococcuspneumoniae neuraminidaseand b-N-acetylglucosaminidase,wereusedforthefirsttime.Sequentialremovalofsugarsfromthe nonreducingterminalsoftheglycansbytheglycosidasesledtorational,ifpartial, proposalsforoligosaccharidesequence.Additionalinformationwasobtainedbymild acidhydrolysisforfragmentsequencing,methylationanalysis,andsequentialperiodateoxidation(Smithdegradation).Forthefirsttime,thecommonpresenceof N-acetyllactosamineattheterminiofcomplex-typeasparagine-linkedglycanswas demonstratedandshownunequivocallybyanalysisofthecrystallinedisaccharide. Jeanlozalsosuggestedfromstudieswithalpha1-acidglycoproteinthattheinnercore, linkedtoasparaginedirectly,wascomposedoftwo N-acetylglucosamineandseveral mannoseresidues.AsadditionalproofoftheproposedstructuresJeanlozandhis colleagues,inparticularHariGarg,usedchemicalsynthesis.67 Thecarbodiimide couplingreagentwasemployedextensivelyforthesynthesisofasparagine-linked compoundssuchas b-GlcNAc-N-Asn.Syntheseswerealsodescribedofdisaccharide fragmentssuchas b-GlcNAc-(1 ! 4)-GlcNAcandtrisaccharidessuchas a-Man(1 ! 6)-b-GlcNAc-(1 ! 4)-GlcNAc.Thesewerecoupledtogivethecorresponding asparagine-linkedderivatives.Subsequently,methodsweredevelopedforthesynthesisofO-glycans,basedonthecorestructure a-GalNAc1-Ser.67

LipidIntermediatesinGlycoproteinBiosynthesis

Long-chainisoprenoidalcohols,polyprenolsanddolichols,wereidentifiedinthe 1970sasintermediatesinbiosynthesisofbacterialpolysaccharidesaswellasinthe multistepprocessofproteinglycosylationinplantsandanimals.Thedonorthatinitiates N-linkedglycansynthesisisaGlc3Man9GlcNAc2 structureattachedtothelipiddolichol throughapyrophosphatelinkage.Theenzymesthatbuildupadolichylpyrophosphateintermediatecontainingtwo N-acetylglucosamineresiduesandthefirstfivemannose residuesutilizesugarnucleotidesdirectly.Transferofthelastfourmannoseresiduesand thethreeglucoseresiduesaremediatedbydolichylphosphate-linkedsugars.Progressin thisresearchwashamperedbythelowabundanceofthephosphorylateddolichol intermediatesincellextracts.Jeanlozandhiscolleagues,inparticularChrisWarren andAnnetteHercovicsandinitiallyinaveryproductivecollaborationwithJackStrominger’slaboratoryatHarvard,undertooktheunequivocalchemicalsynthesisofthese stillpoorlycharacterizedmolecules,andtheirutilizationinbiochemicalstudiesfor

comparisonwiththenaturalcompounds(seeforexample, Refs.68–70).Althoughthe workraisedmanydifficultproblems,anovelmethodologywasdevelopedforthefirst facilesynthesisofdolicholphosphateandpyrophosphate,andtheirsugarderivatives. Althoughitwasgenerallyassumedatthetimethatthelipidmoietyinthelipidintermediateswasdolichol,thishadnotbeenestablishedasinsufficientmaterialwasavailable forchemicalcharacterization:similarlytheanomericidentityofthesugarintermediates wasnotknown.Toaddressthesepoints,theradioactivelylabeledlipidintermediates formedintissuessuchascalfpancreasmicrosomeswerecharacterizedbycomparison withthesyntheticcompounds.Usingthisapproach,theformationintissueswas establishedofdolichyl-b-mannosylphosphate,dolichyl-b-glucosylphosphateand dolichyl-b-N-acetylglucosaminylpyrophosphate.Alipid-linkeddi-N-acetylchitobiose structureformedinthemicrosomalfractionwasshownunequivocallytobeidenticalto syntheticdi-N-acetylchitobiosyl-dolichylpyrophosphate.Inatechnical tourdeforce the pyrophosphate-linkedlipidintermediatecontainingasubstantialpartofthenatural Glc3Man9GlcNAc2 lipidintermediatewasprepared.71 Inthiswork,thesyntheticchemistryintheJeanlozlaboratorywenthandinhandwiththebiochemistry,andmadeamajor contributiontounderstandingofthemodeofassemblyoftheasparagine-linked carbohydrates.

LysosomalGlycosidaseDeficiencies

Inthelate1980s,JeanlozandChrisWarren,incollaborationwithBrianWinchester fromtheInstituteofChildHealth,UniversityofLondonandPeterDanielfromthe KennedySchriverofMentalRetardation,Boston,becameinterestedinthelysosomal storagediseasemannosidosis,aswellasinthetoxicosisinducedinsheepbyingestion offoodstuffscontainingthetoxinswainsonine,apowerfulmannosidaseinhibitor.72–75 Inpartthisinterestwaspromptedbytheneedforrelativelylargeamountsof mannose-richoligosaccharidesforchemicalsynthesisofdolicholintermediatesand glycopeptides.Urinefrompatientswithnoorlowlevelsoflysosomalmannosidases isaconvenientsourceofsucholigosaccharides.Theworkunexpectedlyrevealed someinterestingdataonthepatternsofglycancatabolism.Thestructuresofoligosaccharidesaccumulatedandexcretedbymannosidosispatients,aswellasfromcats andcattlegeneticallyaffectedbylossoflysosomalmannosidases,werecharacterized. Inallcases,thestructureswereconsistentwiththeincompletebreakdownofN-linked glycansorbiosyntheticintermediates.Therewereclearinterspeciesdifferences, however.Compoundscontainingacoreofdi-N-acetylchitobiose,insteadofasingle N-acetylglucosamineresiduewereisolatedfromcattleandcatsbutwereabsentin humanmannosidosis.Humantissuesalonecontainalysosomalendo-b-N-acetylglucosaminidase,accountingforthisdifference.Therewerealsomajordifferencesinthe

NATHANSHARONANDR.COLINHUGHES

structuresoftheexcretedoligomannosecompounds,presumablyreflectingdifferencesinsubstratespecificityoflysosomalmannosidasesinthethreespecies.In humanmannosidosis,wherethereisacompletedeficiencyofthemajorlysosomal mannosidase,thestructureandlevelsofthestoredoligosaccharidesappearedtoresult fromtheactionofaminorlysosomalmannosidasewithspecificityforan a-(1 ! 6) linkage.Infelinemannosidosis,aseveredeficiencyoflysosomalmannosidasesleads tostorageofintactMan9GlcNAc2 oligosaccharidesandtheundegradedMan3GlcNAc2 coreofcomplex-typeglycans.Infurtherstudies,thedetectionofabnormal catabolicproductsinplacentawasfoundtoofferapromisingearlydiagnosisof lysosomalmannosidasedeficiency.76

Tumor-CellGlycoproteins

Attheendofthe1960s,therewasconsiderableinterestinemergingevidencethat alteredcellsurfaceglycosylationappearedtobecommoninmalignantandpremalignantepithelialandsomenonepithelialcells.Thepresenceatcellsurfacesoflarge amountsofcarbohydrate-containingmacromoleculeshadpreviouslybeendemonstratedbyhistochemicalstaining.However,theidentityofthesecomponentsandtheir relevancetocarcinogenesiswaspoorlyunderstood.Atthistime,theJeanlozlaboratory,inparticularJohnCodington,beganworkontheglycoconjugatesoftumorcells incollaborationwithBarbaraSanfordoftheMGHPathologyDivision.77–80 Previous workhadshownthatsomesub-linesoftheTA3tumorcell,derivedfromaspontaneousmammaryadenocarcinomaofanA-strainmouse,haveasurfacemembrane enrichedincarbohydrate.Itwasalsoknownthatthesesub-lineshadloststrain specificityandweretransplantableintostrainsofallogeneicmice,thusevading immunologicalrejectionacrossmajorhistocompatibilitybarriers.Sanfordhad shownfurtherthatsuccessfultransplantationoftheTA3sub-linesintoallogeneic micewasmarkedlyreducedbytreatmentofthecellswithneuraminidase.The suggestionwasthatthesecellsescapethehostdefensesystemthroughcellsurface antigenmaskingbyhighlysialylatedcell-surfaceglycoconjugates.In1972,themajor sialylatedglycoconjugateofTA3cellswasisolatedintheJeanlozlaboratoryand calledepiglycanin.Asshownalittlelaterepiglycaninturnedouttobeasurface membrane-associatedmucincontainingatypicalserineandthreonine-richtandemrepeatsequence,atransmembranedomainandacytoplasmicdomain.TheextracellulardomainwasshownbyDirkvandenEijdenandCodingtontobeheavily substitutedwithO-glycans,basedonthecorestructure b-Gal-(1 ! 3)-GalNAc attachedtoserineorthreonineresidues,heavilysubstitutedwithsialylresidues. ImmunoelectronmicroscopyshowedthatepiglycanincoverstheTA3cellsurface withanextendedfilamentouscoat.Crucially,thisglycoproteinwasfoundnottobe

present,orpresentinlowamounts,inTA3tumorsublinesthatcannotgrowin allogeneichosts,offeringstrongcorroborationoftheideathatcellsurfaceepiglycanin stericallyhinderscytotoxicT-cellsfrommountinganimmuneresponseagainstthe tumor.Manytypesofcancercellsarenowknowntopossesslargeconcentrationsof mucin-likesubstancesattheircellsurface.These,likeepiglycanin,arecharacterized bythepresenceofmultiple O-glycosylically-linkedglycansandextendedrod-like conformations.Theevidenceindicatesthatthesestructures,likeepiglycanin,play rolesinhinderingimmunesurveillancemechanismsandincreasingmetastaticpotential.Recently,thehumanorthologueofepiglycaninhasbeenclonedandnamed Muc21.Itisexpressedinmanymalignanttissues,includinglungadenocarcinomas andbreastcancers,andisofmuchcurrentinterest.

Editor,SymposiaOrganizer,andExpertonCarbohydrateNomenclature

TheproductivityofJeanlozisexemplifiedbyhisbibliographyofmorethan400 publications.Heauthoredmanyreviews,whichareoutstandingfortheirclarity, concisestyle,andinterpretation.Healsoeditedseveralbooks,themostnotableof whichis TheAminoSugars,athree-volumetreatisecoeditedwithEndreBalazs.81 He wasparticularlyconcernedwiththenomenclatureofcarbohydratesandwasinstrumentalinresolvingkeyissuesandintroducingmanynewandwell-definedtermssuch ashyaluronanandglycosaminoglycan.82,83 Inhispublications,hewasalwayscareful inusingthefullchemicalnomenclatureofcarbohydrates.Thus,hefavoredtheterm 2-amino-2-deoxy-D-glucosefor N-acetylglucosamine,andalmostcompletelyavoided theuseoftheabbreviation‘‘GlcN.’’Inadditiontohisresearchandteachingactivities atHarvardandelsewherethroughouttheworld,Jeanlozservedonnumerouscommitteesandeditorialboards;amongothers,hewasoneofthefoundersintheearly 1960softhejournal CarbohydrateResearch,thefirstofitskinddevotedtothe subject.

Thecommunityofcarbohydratescientistsisespeciallyindebtedtohimasacentral figureinthesettingupandorganizationoftheInternationalSymposiaonGlycoconjugates.ThefirstoftheseSymposiawasconvenedin1965inSwampscottwith JeanlozasCo-Chairman.HewasalsotheprimemoverinencouraginghisEuropean colleaguestoorganizethesecondandthirdmeetingsinLillein1973andinBrighton in1975,respectively,andwasactiveintheorganizationofthe4thSymposiumon GlycoconjugatesheldatWood’sHole.TogetherwithJohnGregoryheeditedthetwovolumeproceedingsofthisSymposium.84 In1974–1975,Jeanlozwaspresidentofthe NationalSocietyofComplexCarbohydrates.Hewasalsoactiveformanyyearsinthe DivisionofCarbohydrateChemistryoftheAmericanChemicalSociety,ofwhichhe servedasChairman.Hisnumerousachievementshavebroughthimmanynational

R.W.JEANLOZ

NATHANSHARONANDR.COLINHUGHES

andinternationalhonors.TheseincludetheMedaloftheSocie ´ te ´ deChimieBiologiquedeFrance;MedaloftheUniversitydeLie ´ ge;PrixJaubert,UniversityofGeneva; ClaudeS.HudsonAward,AmericanChemicalSociety;DocteurHonorisCausa, UniversityofParis;andrecentlytheAlexandervonHumboldtAward,Germany’s mostprestigiousscientificaward.Posthumously,thesecondeditionof Essentialsin Glycobiology,editedbyAjitVarki etal.andpublishedin2008,isdedicatedtohis memoryandthatofRosalindKornfeld‘‘pioneersintheelucidationofglycan structureandfunction.’’

DedicatedTeacher,AvidSportsman,andInveterateTraveler

ThescopeofJeanloz’sactivities,andtheknowledgeandenthusiasmthathe impartedtohiscolleagues,allcombinedtoinspirehismanystudents.Hewasfor manyyearsatutorwiththeFacultyofArtsandSciencesofHarvardUniversity, retiringfromthisactivityonlyafewmonthsbeforehisdeath.Becauseofhisqualities, hewasabletoattractandinmanycaseskeepableassociatestohislaboratoryand frequentlycontinuedcollaborationswiththemaftertheyleft.Theexcellenttraining theyreceivedfromJeanlozandthecontactsandfriendshipsmadeinhislaboratory exerciseddecisiveinfluenceontheircareers.Hisdemonstrationoftheimportanceof applyingtherigoroustechniquesoforganicchemistrytothesolutionofbiochemical problemswasthemostcrucialpointofthistraining.

TheuniquelycongenialatmosphereintheJeanlozlaboratorythatisremembered withaffectionbythosewhoworkedwithhimwasaidedgreatlybythepresenceofhis charmingwife,Dorothea,anorganicchemist,whocollaboratedwithhimformany years.Inspiteoftheirbusyschedules,DorotheaandRogeralwaystookgreatinterest inthewell-beingoftheirassociates.Jeanloz’spersonalqualitiesandbonvivant characterendearedhimtoallofhiscolleagues.

Jeanlozwasaninveteratetraveler,whotaughtstudentsfromaboutasmany countriesashehadvisited,atotaldifficulttotallyinanycategory.Inhisyounger yearshewasaskilledalpinist,andmademanyoftheclassicalclimbsintheSwiss FrenchAlps.Hewasalsoanexpertskier,asporthecontinuedtoenjoyintohismore advancedyears,oftenaccompaniedbyhisgrandchildren.Jeanlozwasaloverof classicalmusic,andanenthusiasticgardener.Hisloveforplantscameearlyinhislife whenhebroughtbouquetsofalpineflowersfrommountainexpeditions.Hisinterest insportscanbetracedtohischildhood.Attheageof12,hestartedplayingbasketball, asportthathadbeenintroducedintoSwitzerlandbytheAmericanYMCA.Hewasa memberoftheGenevateamthatwasselectedtorepresentSwitzerlandininternationalgames.Laterhebecameakeentennisplayer,andwasafamiliarfigureonthe tenniscourtsoftheMGH,andintheLongwoodCricketClubnearthefamilyhomein

Newton,Massachusetts,wheretheyraisedtheirfourchildrenDanielle,Sylvie,Raymond,andClaude.FormanyofthelateryearsRogerandDorothyenjoyedtimein theirdelightfulsecondhomeinTourettes-sur-LoupinthesouthofFrance,wherethey wereoftengeneroushoststofriendsandcolleagues.

In1986,aSymposiumwasheldtohonorRogerJeanlozaspartofthe8thInternationalSymposiumonGlycoconjugatesinHouston,Texas.Forthisoccasionthe eminentBritishscientistAlbertNeubergerwrote:‘‘His(Jeanloz’s)workischaracterizedbyamasteryofallchemicalandbiologicalmethods,byreliabilityoftheresults obtained,andbycarefulandbalancedinterpretation.Thereishardlyanytopicinthis widefield,whichhehasnottouched,andwhichhasnotbenefitedfromhisresearch. RogerJeanlozhasmadehislaboratoryoneofthefewoutstandingcentersinthefield ofcomplexcarbohydrates.Hiscombinationofsupremechemicalcompetenceand biologicalunderstandingarethehallmarkofhiscareer.’’

RogerJeanlozwillberememberedwithgreataffectionandutmostrespectbyhis manyfriends,colleagues,anddiscipleswherevertheyare.

ListofassociateswhoworkedwithJeanlozattheLaboratoryofCarbohydrate Research:

E.Alpert,J.Alroy,C.Augi,L.SAzaroff,J.Badet,N.Baggett,E.A.Balasz, M.Beppu,A.K.Bhattacharaya,A.Bhattacharyya,V.P.Bhavanandan,P.Biely,K. C.Blieszner,G.Blix,D.J.Bloch,K.J.Bloch,K.J.BlochSr.,C.H.Bolton,A.A. Bothner,M.C.Brown,B.Bugge,R.A.Byrn,G.F.Cahill,M.S.Choudhary,A.-M. Close,J.F.Codington,A.G.Cooper,T.Dalianis,P.F.Daniel,D.Daniels,D.M. Darby,H.R.Das,E.A.Davidson,P.Degand,M.R.Dick,F.DuBois,D.vanden Ejnden,J.V.Ellard,N.A.Evans,E.H.Eylar,N.E.Fayaz-ud-Din,H.M.Flowers,R. Fricke,D.M.Frim,T.C.Fuller,C.Gansser,H.G.Garg,J.DeGasperi,M.C.Glick, D.Gminsky,A.M.Golovchenko,Y.Goussault,P.H.Gross,M.Gut,M.A.Gvalambor,P.Gyorgy,S.Hakomori,H.vanHalbeeck,A.M.Halford,M.D.A.Halford, M.H.Halford,A.Hallen,V.B.Hatcher,F.Heatley,A.Herscovics,O.Hoshino,S.A. Houssain,R.C.Hughes,M.R.Jahnke,L.F.James,D.Jeanloz,A.Jimbo,M.Z.Jones, R.Kaifu,R.L.Katzman,R.D.Kilker,W.Klaffke,G.Klein,E.H.Kolodny,Y. Konami,J.Koscielak,J.J.Lamar,G.Lamblin,L.A.Lampert,D.W.Laske,R.D. Lasky,M.L.Laver,M.M.Lee,N.Lee,C.Levrat,M.Lhermitte,K.B.Linsley,E. Lisowska,C.M.Liu,I.Y.Liu,T.Matsumoto,M.D.Maxfield,J.W.McArthur,D. Medrek,C.Merser,M.-L.Milat,D.K.Miller,S.C.Miller,T.Mitvedt,KMiyai,Y. Mizuno,J.D.Moore,J.H.G.M.Mutsaers,S.Nakabayashi,T.E.Nash,E.Salomon, R.Naves,N.Nikrui,H.VonNocolai,T.Osawa,P.D.Palmer,M.Parquet,P. Perchfelides,J.M.Petit,J.R.Poortmans,D.Power,E.S.Rachaman,S.S.Raghavan, A.M.C.Rapin,E.J.SRathke,V.N.Reinhold,G.P.Roberts,A.A.Rossini,S.W.

R.W.JEANLOZ

16

NATHANSHARONANDR.COLINHUGHES

Rostad,P.Roussel,S.Sadeh,M.M.ElSadek,B.H.Sanford,S.Santikarn,W.Sasak, D.M.Schmid,K.Schmid,A.S.Schmit,D.Schwarzenbach,G.O.H.Schwarzmann,J. F.Scott,M.Shaban,M.Shalev,N.Sharon,C.Silber,P.Sinay ¨ ,H.S.Slayte,M.Spinola, R.G.Spiro,G.F.Springer,D.K.Stearns,R.L.Stephens,P.F.Stoffyn,G.Strecker,S. Suzuki,Z.Tarasiejska-Glazer,P.Thoma,J.S.Tkacz,M.Tomoda,M.Tre ´ me ` ege,R.B. Trimble,B.Tuttle,Nasir-ud-Din,J.R.Vercellotti,A.Veyrie ` res,J.F.G.Vliegenthart,R. Vrba,E.Walker,C.D.Warren,H.Wecyer,J.F.Wedgwood,N.R.Williams,B. Winchester,J.K.Wold,I.Yamashina,T.Yamazaki,J.Yoshikawa,N.Zamchek,U. Zehavi,F.Zilliken.

Theworkofonlyafewofthemorethantwohundredcolleaguesandcollaborators ofJeanlozlistedherecouldbedetailedwithinthescopeofthistribute.

NathanSharon R.ColinHughes

References

1.K.-H.Meyer,E.Preiswerk,andR.W.Jeanloz, Helv.Chim.Acta,24(1941) 1395–1409.

2.R.Jeanloz,The ` sedeDocteuresSciencesChimiques(1943)del’Universite ´ de Gene ` ve.

3.R.Jeanloz,D.A.Prins,andT.Reichstein, Experientia,1(1945)1–2.

4.D.A.PrinsandR.W.Jeanloz, Ann.Rev.Biochem.,17(1948)67–96.

5.R.Jeanloz,H.G.Fletcher,Jr.,andC.S.Hudson, J.Am.Chem.Soc.,70(1948) 4052–4054.

6.R.Jeanloz,H.G.Fletcher,Jr.,andC.S.Hudson, J.Am.Chem.Soc.,70(1948) 4055–4057.

7.R.W.Jeanloz,G.R.Barker,andM.V.Lock, Nature,167(1951)42–43.

8.R.W.JeanlozandH.G.Fletcher,Jr., Adv.Carbohydr.Chem.,6(1951)135–174.

9.O.Hechter,R.P.Jacobsen,R.Jeanloz,H.Levy,C.W.Marshall,andG.Pincus, Arch.Biochem.,25(1950)457–460.

10.O.Hechter,R.P.Jacobsen,V.Schenker,H.Levy,R.W.Jeanloz,W.Marshall, andG.Pincus, Endocrinology,52(1953)679–691.

11.H.Levy,R.W.Jeanloz,C.W.Marshall,R.P.Jacobsen,O.Hechter,V.Schenker, andG.Pincus, J.Biol.Chem.,203(1953)433–451.

12.R.W.Jeanloz,H.Levy,R.P.Jacobsen,O.Hechter,V.Schenker,andG.Pincus, J.Biol.Chem.,203(1953)453–461.

R.W.JEANLOZ

13.A.S.Meyer,R.W.Jeanloz,andG.Pincus, J.Biol.Chem.,203(1953)463–468.

14.H.Levy,R.W.Jeanloz,R.P.Jacobsen,O.Hechter,V.Schenker,andG.Pincus, J.Biol.Chem.,211(1954)867–881.

15.R.W.JeanlozandE.Forchielli, J.Biol.Chem.,188(1951)361–369.

16.R.W.JeanlozandE.Forchielli, J.Biol.Chem.,190(1951)537–546.

17.R.JeanlozandE.Forchielli, Helv.Chim.Acta,33(1950)1690–1697.

18.R.W.Jeanloz, Adv.Carbohydr.Chem.,13(1958)189–214.

19.R.W.JeanlozandC.Gansser, J.Am.Chem.Soc.,79(1957)2583–2585.

20.R.W.Jeanloz, J.Am.Chem.Soc.,76(1954)558–562.

21.R.W.Jeanloz, J.Org.Chem.,26(1961)905–908.

22.P.J.StoffynandR.W.Jeanloz, J.Am.Chem.Soc.,76(1954)561–562.

23.R.W.JeanlozandP.J.Stoffyn, J.Am.Chem.Soc,76(1954)5682–5684.

24.P.J.StoffynandR.W.Jeanloz, J.Am.Chem.Soc.,80(1958)5690–5692.

25.D.K.Stearns,R.G.Naves,andR.W.Jeanloz, J.Org.Chem.,26(1961) 901–905.

26.P.J.StoffynandR.W.Jeanloz, J.Am.Chem.Soc.,76(1954)563–564.

27.R.W.JeanlozandH.M.Flowers, Carbohydr.Res.,2(1966)411–413.

28.Nasir-ud-Din,andR.W.Jeanloz, Carbohydr.Res.,28(1973)243–251.

29.P.J.StoffynandR.W.Jeanloz, Arch.Biochem.,52(1954)373–379.

30.R.W.Jeanloz, Chimia,7(1953)292.

31.R.W.JeanlozandH.M.Flowers, J.Am.Chem.Soc.,84(1962)3030–3126.

32.H.M.FlowersandR.W.Jeanloz, Biochemistry,3(1964)123–125.

33.R.W.Jeanloz, Adv.Enzymol.Relat.AreasMol.Biol.,25(1963)433–456.

34.P.J.StoffynandR.W.Jeanloz, J.Biol.Chem.,235(1960)2507–2510.

35.S.I.HakomoriandR.W.Jeanloz, J.Biol.Chem.,236(1961)2827–2834.

36.S.HakomoriandR.W.Jeanloz, J.Biol.Chem.,239(1964)PC3606–PC3607.

37.S.I.Hakomori,J.Koscielak,K.J.Bloch,andR.W.Jeanloz, J.Immunol.,98 (1967)31–38.

38.S.I.Hakomori,J.Koscielak,andR.W.Jeanloz, Immunochemistry,5(1968) 441–455.

39.H.M.FlowersandR.W.Jeanloz, J.Org.Chem.,28(1963)1377–1379.

40.H.M.FlowersandR.W.Jeanloz, J.Org.Chem.,28(1963)1564–1567.

41.H.M.FlowersandR.W.Jeanloz, J.Org.Chem.,28(1963)2983–2986.

42.T.OsawaandR.W.Jeanloz, Carbohydr.Res. (1965)181–186.

43.R.W.Jeanloz,D.M.Schmid,andP.J.Stoffyn, J.Am.Chem.Soc.,79(1957) 2586–2590.

44.R.W.Jeanloz,E.Walker,andP.Sinay, Carbohydr.Res.,6(1968)184–196.

NATHANSHARONANDR.COLINHUGHES

45.T.Osawa,P.Sinay,M.Halford,andR.W.Jeanloz, Biochemistry,8(1969) 3369–3375.

46.P.Sinay ¨ andR.W.Jeanloz, Carbohydr.Res.,10(1969)189–196.

47.P.Sinay,M.D.Halford,M.S.Choudhary,P.H.Gross,andR.W.Jeanloz, J. Biol.Chem.,247(1972)391–397.

48.Y.Konami,T.Osawa,andR.W.Jeanloz, Biochemistry,10(1971)192–196.

49.A.Veyrie ` resandR.W.Jeanloz, Biochemistry,9(1970)4153–4159.

50.O.Hoshino,U.Zehavi,P.Sinay ¨ ,andR.W.Jeanloz, J.Biol.Chem.,247(1972) 381–390.

51.N.SharonandR.W.Jeanloz, Experientia,20(1964)253–254.

52.N.Sharon,T.Osawa,H.M.Flowers,andR.W.Jeanloz, J.Biol.Chem.,241 (1966)223–230.

53.R.L.KatzmanandR.W.Jeanloz, Science,166(1969)758–759.

54.R.L.KatzmanandR.W.Jeanloz, J.Biol.Chem.,248(1973)50–55.

55.R.L.KatzmanandR.W.Jeanloz,inE.A.Balazs,(Ed.), TheChemistryand BiochemistryoftheIntracellularMatrix,Vol.1,pp.149–159.

56.R.L.Katzman,E.Lisowska,andR.W.Jeanloz, Biochem.J.,119(1970)17–19.

57.Z.TarasiejskaandR.W.Jeanloz, J.Am.Chem.Soc.,79(1957)2660.

58.Z.TarasiejskaandR.W.Jeanloz, J.Am.Chem.Soc.,79(1957)4215–4218.

59.R.W.Jeanloz,Z.Tarasiejska-Glazer,andD.A.Jeanloz, J.Org.Chem.,26(1961) 537–541.

60.R.W.JeanlozandD.A.Jeanloz, J.Org.Chem.,26(1961)537–546.

61.R.W.JeanlozandA.M.C.Rapin, J.Org.Chem.,28(1963)2978–2986.

62.N.SharonandR.W.Jeanloz, J.Biol.Chem.,235(1960)1–5.

63.E.H.EylarandR.W.Jeanloz, J.Biol.Chem.,237(1962)622–628.

64.E.H.EylarandR.W.Jeanloz, J.Biol.Chem.,237(1962)1021–1025.

65.R.G.Spiro, J.Biol.Chem.,237(1962)646–652.

66.R.G.Spiro, J.Biol.Chem.,239(1964)567–573.

67.H.G.GargandR.W.Jeanloz, Adv.Carbohydr.Chem.Biochem.,43(1985) 135–201.

68.C.D.WarrenandR.W.Jeanloz, MethodsEnzymol.,50(1978)122–137.

69.Y.Goussault,S.Nakabayashi,C.D.Warren,B.Bugge,andR.W.Jeanloz, Carbohydr.Res.,179(1988)381–392.

70.J.F.Wedgewood,C.D.Warren,R.W.Jeanloz,andJ.L.Strominger, Proc.Natl. Acad.Sci.USA,71(1974)5022–5026.

71.C.D.Warren,I.Y.Liu,A.Herscovics,andR.W.Jeanloz, J.Biol.Chem.,250 (1975)8069–8078. 18

R.W.JEANLOZ

72.C.D.Warren,A.S.Schmit,andR.W.Jeanloz, Carbohydr.Res.,116(1983) 171–182.

73.S.Sadeh,C.D.Warren,P.F.Daniel,B.Bugge,L.F.James,andR.W.Jeanloz, FEBSLett.,163(1983)104–109.

74.C.D.Warren,P.F.Daniel,B.Bugge,J.E.Evans,L.F.James,andR.W.Jeanloz, J.Biol.Chem.,263(1988)15041–15049.

75.R.DeGasperi,S.alDaher,P.F.Daniel,B.G.Winchester,R.W.Jeanloz,and C.D.Warren, J.Biol.Chem.,266(1991)16556–16563.

76.C.D.Warren,J.Alroy,B.Bugge,P.F.Daniel,S.S.Raghavan,E.H.Kolodny, J.J.Lamar,andR.W.Jeanloz, FEBSLett.,195(1986)247–252.

77.J.F.CodingtonandR.W.Jeanloz, Z.Klin.Chem.Klin.Biochem.,9(1971)61.

78.J.F.Codington,B.H.Sanford,andR.W.Jeanloz, J.Natl.CancerInst.,51(1973) 585–591.

79.J.F.Codington,K.B.Linsley,R.W.Jeanloz,T.Irimura,andT.Osawa, Carbohydr.Res.,40(1975)171–182.

80.D.H.VandenEijnden,N.A.Evans,J.F.Codington,V.Reinhold,C.Silber,and R.W.Jeanloz, J.Biol.Chem.,254(1979)12153–12159.

81.R.W.JeanlozandE.A.Balazs, TheAminoSugars (1966)AcademicPress,New York,1ADistributionandBiologicalRoles,591pp,Vol.2A;Chemistryofthe AminoSugars,827pp,Vol.2B;MetabolismandInteractions.

82.R.W.Jeanloz, ArthritisRheum.,3(1960)233–237.

83.E.A.Balazs,T.C.Laurent,andR.W.Jeanloz, Biochem.J.,235(1986)903.

84.J.D.GregoryandR.W.Jeanloz, GlyconjugateResearchProceedingofthe FourthInternationalSymposiumonGlycoconjugates (1797)AcademicPress, NewYork,Vol.1,pp.1–571;Vol.2,pp.578–1103.

Another Random Scribd Document with Unrelated Content

Turn static files into dynamic content formats.

Create a flipbook
Issuu converts static files into: digital portfolios, online yearbooks, online catalogs, digital photo albums and more. Sign up and create your flipbook.