Peptide Chemistry and Drug Design

338 Pages·2015·4.02 MB·English

by  Shaik Zaheer Ahmed

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PEPTIDE CHEMISTRY
AND DRUG DESIGN
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PEPTIDE CHEMISTRY
AND DRUG DESIGN
Edited by
BENM.DUNN
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Copyright©2015byJohnWiley&Sons,Inc.Allrightsreserved
PublishedbyJohnWiley&Sons,Inc.,Hoboken,NewJersey
PublishedsimultaneouslyinCanada
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LibraryofCongressCataloging-in-PublicationData:
PeptideChemistryandDrugDesign/editedbyBenM.Dunn.
p.;cm.
Includesbibliographicalreferencesandindex.
Summary:“Thisbookdetailsmanyoftheproblemsandsuccessesofpeptidesaspotentialdrugs”–
Providedbypublisher.
ISBN978-0-470-31761-7(hardback)
I.Dunn,BenM.,editor.
[DNLM:1.Peptides–chemistry.2.DrugDesign.3.PharmaceuticalPreparations.QU68]
RM301.25
615.1′9–dc23
2014040280
CoverimagecourtesyofDavidCraikandQuentinKaas,UniversityofQueensland
Typesetin10/12ptTimesLTStdbyLaserwordsPrivateLimited,Chennai,India
PrintedintheUnitedStatesofAmerica
10987654321
1 2015
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CONTENTS
Preface xi
ListofContributors xv
1 PeptideTherapeutics 1
NaderFotouhi
1.1 HistoryofPeptidesasDrugs, 1
1.2 FactorsLimitingtheUseofPeptidesintheClinic, 2
1.3 AdvancesthathaveStimulatedtheUseofPeptidesasDrugs, 3
1.4 DevelopmentofPeptideLibraries, 4
1.5 ModificationofPeptidestoPromoteStabilityandCellEntry, 6
1.6 TargetingPeptidestoSpecificCells, 7
1.7 FormulationstoImproveProperties, 7
References, 8
2 MethodsforthePeptideSynthesisandAnalysis 11
JuditTulla-Puche,AymanEl-Faham,AthanassiosS.Galanis,
EliandredeOliveira,AikateriniA.Zompra,andFernandoAlbericio
2.1 Introduction, 11
2.2 SolidSupports, 13
2.3 Linkers, 15
2.4 ProtectingGroups, 17
2.4.1 TheSpecialCaseofCysteine, 18
2.5 MethodsforPeptideBondFormation, 20
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vi CONTENTS
2.5.1 Peptide-BondFormationfromCarbodiimide-Mediated
Reactions, 20
2.5.2 Peptide-BondFormationfromPreformedSymmetric
Anhydrides, 22
2.5.3 Peptide-BondFormationfromAcidHalides, 23
2.5.4 Peptide-BondFormationfromPhosphoniumSalt-Mediated
Reactions, 23
2.5.5 Peptide-BondFormationfromAminium/UroniumSalt-Mediated
Reactions, 24
2.6 Solid-PhaseStepwiseSynthesis, 26
2.6.1 LongPeptides, 27
2.7 SynthesisinSolution, 29
2.7.1 N𝛼 ProtectionoftheN-TerminalAminoAcidDerivativeor
Fragment, 30
2.7.2 Carboxy-GroupProtectionoftheC-terminalAmino-Acid
DerivativeorFragment, 31
2.7.3 PeptideBondFormation, 34
2.8 HybridSynthesis–CombinationofSolidandSolutionSynthesis, 34
2.8.1 ClassicalSegmentCondensation, 35
2.8.2 NativeChemicalLigation, 36
2.9 CyclicPeptides, 37
2.10Depsipeptides, 38
2.11SeparationandPurificationofPeptides, 40
2.11.1 Gel-FiltrationChromatography, 41
2.11.2 Ion-ExchangeChromatography, 41
2.11.3 Reverse-PhaseHighPerformanceLiquidChromatography, 42
2.12CharacterizationofPeptidesThroughMassSpectrometry, 43
2.12.1 IonizationSource, 44
2.12.2 MassAnalysers, 45
2.12.3 PeptideFragmentation, 49
2.12.4 QuantificationbyMS, 51
2.13Conclusions, 52
Acknowledgments, 53
Abbreviations, 53
References, 56
3 PeptideDesignStrategiesforG-ProteinCoupledReceptors
(GPCRs) 75
AnamikaSinghandCarrieHaskell-Luevano
3.1 Introduction, 75
3.2 ClassificationofGPCRs, 76
3.3 CatalogofPeptide-ActivatedG-ProteinCoupledReceptors, 77
3.4 StructureofGPCRs:CommonFeatures, 77
3.4.1 CrystalStructures, 77
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CONTENTS vii
3.5 GPCRActivation, 93
3.5.1 Ligand(Peptide)BindingandReceptorActivation, 94
3.5.2 CommonStructuralChangesamongGPCRs, 95
3.5.3 G-ProteinCoupledIntracellularSignalingPathways, 95
3.6 StructureandFunctionofPeptideHormones, 98
3.7 DesignApproachesforGPCRSelectivePeptideLigands, 98
3.7.1 Structure–ActivityRelationship(SAR)Studies, 99
3.7.2 ChimericPeptideAnalogs, 103
3.7.3 CombinatorialLibraries, 103
3.7.4 Three-Dimensional(3D)GPCRHomologyMolecular
Modeling, 104
3.8 Conclusions, 105
Acknowledgments, 105
References, 106
4 Peptide-BasedInhibitorsofEnzymes 113
AnnaKnapinska,SabrinaAmar,TristaK.Robichaud,and
GreggB.Fields
4.1 Introduction, 113
4.2 Angiotensin-ConvertingEnzymeandNeprilysin/Neutral
Endopeptidase, 114
4.3 PeptideInhibitorsoftheHIV-1ViralLifeCycle, 117
4.4 MatrixMetalloproteinases, 118
4.5 AntraxLethalFactorInhibitionbyDefensins, 125
4.6 Kinases, 127
4.7 Glycosyltransferases(Oligosaccharyltransferases), 131
4.8 TelomeraseInhibitors, 134
4.9 Tyrosinase, 138
4.10Peptidyl-ProlylIsomerase, 140
4.11HistoneModifyingEnzymes, 143
4.11.1 HistoneDeacetylase, 144
4.11.2 HistoneMethyl-Transferase, 145
4.12PuttingitallTogether:PeptideInhibitorApplicationsinSkinCare, 146
4.13StrategiesfortheDiscoveryofNovelPeptideInhibitors, 147
Acknowledgments, 148
References, 148
5 DiscoveryofPeptideDrugsasEnzymeInhibitorsandActivators 157
Jeffrey-TriNguyenandYoshiakiKiso
5.1 Introduction, 157
5.1.1 PeptideResidueNomenclature, 158
5.1.2 CommonMethodsofDrugDesign, 159
5.1.3 PhasesofDrugDevelopment, 163
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