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1、PeptideMimicsofBacterialPolysaccharides:PotentialforDiscriminatingVaccinesSilviaBorrelli,MargaretA.Johnson,RehanaB.Hossany,andB.MarioPinto*DepartmentofChemistry,SimonFraserUniversity,Burnaby,BritishColumbia,V5A1S6,CanadaAnalternativeapproachtovaccinedesignistheuseofmolec
2、ulesthatmimictheimmunogenicelementofinterest.Carbohydrate-mimeticpeptides,assurrogateligandsfortraditionalcarbohydratevaccines,havethepotentialtogeneratemorediscriminatingimmuneresponses.Inthiscontext,peptide-mimicsofGroupAandBStreptococcus,andShigellaflexneriYpolysaccha
3、rideshavebeenidentified,theirinteractionwithanti-carbohydrateantibodiesstudiedbyNMRtechniques,molecularmodeling,orX-raycrystallography,andcomparedtothecorrespondinginteractionswithpolysaccharideorcomponentoligosaccharides.Theimmunologicalresponsesofthecarrier-proteinconj
4、ugatesofpeptidemimicscorrespondingtoGroupAandBStreptococcuspolysaccharideshavebeeninvestigatedinmice,andyieldedcrossreactiveresponsesagainstthepolysaccharides.Aworkinghypothesisthatpeptideturn-conformationspresentimportantepitopesisadvanced.22c20e00ce61b685609234e113b949
5、ff9f.docPrinted2021/6/21IntroductionBacterialinfectionsarestillamajorglobalhealthproblem(1,2).Antimicrobialtherapeutics,althoughverysuccessful,arenottheidealsolutiontohandlemanyofthebacterialinfectionstoday.Drugresistanceisrathercommon,andthedevelopmentofnew,effectivedru
6、gsisstillexpensive(2,3).Inaddition,theimpactonsocietyfromthecostofdrugadministrationandthe“down-time”duetosicknessisasignificantissue.Thus,thesearchfornew,effectivevaccinestopreventthesetypesofinfectionsisstillanenviablegoal,especiallyindevelopingcountries(1-3).Thehostre
7、spondstoabacterialinfectionbytriggeringaspecificimmuneresponse,bothB-cellorhumoral,withtheproductionofspecificantibodies,andTcellorcellular,withaclearroleofT-cellsinimmunologicalmemoryfunctions.Theidentificationofantigenscapableofinducingprotectiveandlonglastingimmunityi
8、sthemajorgoalforeffectivevaccinedevelopment(4).Thesurfaceofmanybacterialspeciesiscoveredbyseveralstruct
