Total Chemical Synthesis of Proteins

614 Pages·2021·19.25 MB·English

by  Lei Liu (editor), Ashraf Brik (editor), Philip Dawson (editor)

TotalChemicalSynthesisofProteins
Total Chemical Synthesis of Proteins
Edited by
Ashraf Brik, Philip Dawson, and Lei Liu
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v
Contents
Preface xvii
1 CharacterizationofProteinMoleculesPreparedbyTotal
ChemicalSynthesis 1
StephenB.H.Kent
1.1 Introduction 1
1.2 ChemicalProteinSynthesis 2
1.3 CommentsonCharacterizationofSyntheticProteinMolecules 8
1.3.1 Homogeneity 8
1.3.2 AminoAcidSequence 9
1.3.3 ChemicalAnalogues 10
1.3.4 LimitationsofSPPS 10
1.3.5 FoldingasaPurificationStep 10
1.4 Summary 12
References 12
2 AutomatedFastFlowPeptideSynthesis 17
MarkD.Simon,AlexanderJ.Mijalis,KyleA.Totaro,DanielDunkelmann,
AlexanderA.Vinogradov,ChiZhang,YutaMaki,JustinM.Wolfe,Jessica
Wilson,AndreiLoas,andBradleyL.Pentelute
2.1 Introduction 17
2.2 Results 19
2.2.1 Summary 19
2.2.1.1 MechanicalPrinciples 20
2.2.1.2 ChemicalPrinciples 20
2.2.1.3 UserInterfacePrinciples 20
2.2.1.4 DataAnalysisMethod 20
2.2.1.5 Outcome 21
2.2.2 First-generationAutomatedFastFlowPeptideSynthesis 21
2.2.2.1 KeyFindings 21
2.2.2.2 DesignofFirst-generationAFPS 21
2.2.2.3 CharacterizationofFirst-generationAFPS 23
2.2.3 Second-generationAutomatedFastFlowPeptideSynthesis 24
vi Contents
2.2.3.1 KeyFindings 24
2.2.3.2 DesignofSecond-generationAFPS 24
2.2.3.3 CharacterizationandUseofSecond-generationAFPS 26
2.2.4 Third-generationAutomatedFastFlowPeptideSynthesis 32
2.2.4.1 KeyFindings 32
2.2.4.2 DesignofThird-generationAFPS 34
2.2.4.3 CharacterizationofThird-generationAFPS 39
2.2.4.4 ReagentStabilityStudy 43
2.2.5 Fourth-generationAutomatedFastFlowPeptideSynthesis 45
2.2.5.1 KeyFindings 45
2.2.5.2 EffectofSolventonFastFlowSynthesis 45
2.2.5.3 DesignandCharacterizationofFourth-generationAFPS 45
2.3 Conclusions 49
Acknowledgments 53
References 53
3 N,S-andN,Se-AcylTransferDevicesinProteinSynthesis 59
VincentDiemer,JenniferBouchenna,FlorentKerdraon,VangelisAgouridas,
andOlegMelnyk
3.1 Introduction 59
3.2 N,S-andN,Se-AcylTransferDevices:GeneralPresentation,Reactivity
andStatisticalOverviewofTheirUtilization 61
3.2.1 GeneralPresentationofN,S-andN,Se-AcylTransferDevices 61
3.2.2 RelativeReactivityofN,S-andN,Se-AcylTransferDevices 63
3.2.3 AStatisticalOverviewoftheSyntheticUseofN,S-andN,Se-Acyl
TransferDevicesforProteinTotalChemicalSynthesis 64
3.3 PreparationofSEA/SeEAoffandSEAlidePeptides 68
3.3.1 PreparationofSEAandSeEAPeptides 68
3.3.2 PreparationofSEAlidePeptides 70
3.4 Redox-controlledAssemblyofBiotinylatedNK1Domainofthe
HepatocyteGrowthFactor(HGF)UsingSEAandSeEAChemistries 71
3.5 TheTotalChemicalSynthesisofGM2-APUsingSEAlide-based
Chemistry 75
3.6 Conclusion 79
References 80
4 ChemicalSynthesisofProteinsThroughNativeChemical
LigationofPeptideHydrazides 87
ChaoZuo,XiaodanTan,XianglongTan,andLeiLiu
4.1 Introduction 87
4.2 DevelopmentofPeptideHydrazide-basedNativeChemicalLigation 88
4.2.1 ConversionofPeptideHydrazidetoPeptideAzide 88
4.2.2 AcylAzide-basedSolid-phasePeptideSynthesis 88
4.2.3 AcylAzide-basedSolution-phasePeptideSynthesis 89
4.2.4 TheTransesterificationofAcylAzide 90
Contents vii
4.2.5 DevelopmentofPeptideHydrazide-basedNativeChemicalLigation
90
4.3 OptimizationofPeptideHydrazide-basedNativeChemicalLigation
91
4.3.1 PreparationofPeptideHydrazides 91
4.3.1.1 2-Cl-Trt-ClResin 91
4.3.1.2 PeptideHydrazidesfromExpressedProteins 92
4.3.1.3 Sortase-mediatedHydrazideGeneration 93
4.3.2 ActivationMethodsofPeptideHydrazide 94
4.3.2.1 KnorrPyrazoleSynthesis 94
4.3.2.2 ActivationinTFA 94
4.3.3 LigationSitesofPeptideHydrazide 95
4.3.4 MultipleFragmentLigationBasedonPeptideHydrazide 96
4.3.4.1 N-to-CSequentialLigation 96
4.3.4.2 ConvergentLigation 96
4.3.4.3 One-potLigation 96
4.4 ApplicationofPeptideHydrazide-basedNativeChemicalLigation 99
4.4.1 PeptideDrugsandDiagnosticTools 99
4.4.1.1 PeptideHydrazidesforCyclicPeptideSynthesis 99
4.4.1.2 ScreeningforDPeptideInhibitorsTargetingPD-L1 99
4.4.1.3 ChemicalSynthesisofDCAFforTargetedAntibodyBlocking 101
4.4.1.4 PeptideToxins 101
4.4.2 SynthesisandApplicationofTwo-photonActivatableChemokine
CCL5 102
4.4.3 ProteinswithPosttranslationalModification 103
4.4.3.1 TheSynthesisofGlycosylation-modifiedFull-lengthIL-6 103
4.4.3.2 TheChemicalSynthesisofEPO 105
4.4.3.3 ChemicalSynthesisofHomogeneousPhosphorylatedp62 105
4.4.3.4 ChemicalSynthesisofK19,K48Bi-acetylatedAtg3Protein 105
4.4.4 UbiquitinChains 108
4.4.4.1 SynthesisofK27-linkedUbiquitinChains 108
4.4.4.2 SynthesisofAtypicalUbiquitinChainsbyUsinganIsopeptide-linkedUb
Isomer 109
4.4.4.3 SynthesisofAtypicalUbiquitinChainsUsinganIsopeptide-linkedUb
Isomer 109
4.4.5 ModifiedNucleosomes 110
4.4.5.1 SynthesisofDNA-barcodedModifiedNucleosomeLibrary 110
4.4.5.2 SynthesisofModifiedHistoneAnalogswithaCysteine
Aminoethylation-assistedChemicalUbiquitinationStrategy 111
4.4.5.3 SynthesisofUbiquitylatedHistonesforExaminationofthe
DeubiquitinationSpecificityofUSP51 111
4.4.6 MembraneProteins 112
4.4.7 Mirror-imageBiologicalSystems 112
4.5 SummaryandOutlook 113
References 114
viii Contents
5 ExpandingNativeChemicalLigationMethodologywith
SyntheticAminoAcidDerivatives 119
EmmaE.Watson,LaraR.Malins,andRichardJ.Payne
5.1 NativeChemicalLigation 120
5.2 DesulfurizationChemistries 120
5.3 AsparticAcid(Asp,D) 122
5.4 GlutamicAcid(Glu,E) 124
5.5 Phenylalanine(Phe,F) 125
5.6 Isoleucine(Ile,I) 127
5.7 Lysine(Lys,K) 130
5.8 Leucine(Leu,L) 133
5.9 Asparagine(Asn,N) 135
5.10 Proline(Pro,P) 138
5.11 Glutamine(Gln,Q) 139
5.12 Arginine(Arg,R) 139
5.13 Threonine(Thr,T) 140
5.14 Valine(Val,V) 142
5.15 Tryptophan(Trp,W) 144
5.16 ApplicationofSelenocysteine(Sec)toLigationChemistry 146
5.17 AsparticAcid(Asp,D) 147
5.18 GlutamicAcid(Glu,E) 148
5.19 Phenylalanine(Phe,F) 149
5.20 Leucine(Leu,L) 151
5.21 Proline(Pro,P) 151
5.22 Serine(Ser,S) 153
References 155
6 PeptideLigationsatStericallyDemandingSites 161
YingluWangandSuweiDong
6.1 Introduction 161
6.2 LigationsUsingThioesters 162
6.2.1 ExogenousAdditive-promotedLigations 162
6.2.2 LigationsUsingReactiveThioesters 167
6.2.3 InternalActivationStrategyinPeptideLigations 169
6.3 LigationsUsingOxo-esters 170
6.4 PeptideLigationsBasedonSelenoesters 170
6.5 Microfluidics-promotedNCL 175
6.6 RepresentativeApplicationsinProteinSynthesis 178
6.7 SummaryandOutlook 181
References 181
7 ControllingSegmentSolubilityinLargeProtein
Synthesis 185
RileyJ.Giesler,JamesM.Fulcher,MichaelT.Jacobsen,andMichaelS.Kay
7.1 SolventManipulation 185
Contents ix
7.2 IsoacylStrategy 187
7.3 SemipermanentSolubilizingTags 191
7.3.1 N-orC-TerminalSolubilizing“Tails” 192
7.3.2 ReversibleBackboneModificationsasSolubilizingTags 194
7.3.3 BuildingBlockSolubilizingTags 195
7.3.4 ExtendableSide-chain-basedSolubilizingTags 195
References 198
8 TowardHPLC-freeTotalChemicalSynthesisofProteins 211
PhucUngandOliverSeitz
8.1 Introduction 211
8.1.1 CaptureandReleasePurification 212
8.1.2 Solid-phaseChemicalLigations(SPCL) 212
8.2 SynthesisofPeptideSegmentsforNativeChemicalLigation 213
8.2.1 HPLC-freePreparationofN-terminalPeptideSegmentsforNCL 213
8.2.2 HPLC-freePreparationofC-terminalPeptideSegmentsforNCL 217
8.3 SynthesisofProteinsUsingtheHis Tag 220
6
8.3.1 ReversibleHis -basedCaptureTags 220
6
8.3.2 His -basedImmobilizationforC-to-NAssemblyofCrambin 221
6
8.3.3 His -basedImmobilizationforAssemblyofProteinsonMicrotiter
6
Plates 222
8.3.4 His andHydrazideTagsforSequentialN-to-CCaptureand
6
Release 225
8.4 SynthesisofProteinsviaOximeFormation 227
8.4.1 ReversibleOxime-basedCaptureTags 227
8.4.2 Oxime-basedImmobilizationforN-to-CSolid-phaseChemical
Ligations 227
8.4.3 Oxime-basedImmobilizationforC-to-NSolid-phaseChemical
Ligations 233
8.4.4 Oxime-basedC-to-NSolid-phaseChemicalLigations 237
8.5 SynthesisofProteinsviaHydrazoneFormation 238
8.5.1 ReversibleHydrazone-basedCaptureTags 238
8.5.2 Hydrazone-basedImmobilizationforAssemblyofProteinsonMicrotiter
Plates 239
8.6 SynthesisofProteinsUsingClickChemistry 242
8.6.1 Click-basedImmobilizationforN-to-CSolid-phasePeptideLigations
UsingaProtectedAlkyne 242
8.6.2 Click-basedImmobilizationforN-to-CSolid-phasePeptideLigations
UsingaSeaGroup 243
8.7 SynthesisofProteinsUsingtheKAHALigation 244
8.7.1 TheKAHALigation 244
8.7.2 HPLC-freeSynthesisofProteinsUsingtheKAHALigation 245
8.8 SynthesisofProteinsUsingPhotocleavableTags 246
8.8.1 SynthesisofProteinsUsingaPhotocleavableBiotin-basedPurification
Tag 246
x Contents
8.8.2 SynthesisofProteinsUsingaPhotocleavableHis -basedPurification
6
Tag 247
8.9 Conclusion 249
References 251
9 Solid-phaseChemicalLigation 259
SkanderA.Abboud,AgnèsF.Delmas,andVincentAucagne
9.1 Introduction 259
9.1.1 ThePromisesofSolidPhaseChemicalLigation(SPCL) 259
9.1.2 ChemicalLigationReactionsUsedforSPCL 260
9.1.3 KeyRequirementsforaSPCLStrategy 261
9.2 SPCLintheC-to-NDirection 262
9.2.1 TemporaryMaskingGroupstoEnableIterativeLigations 262
9.2.2 LinkersforC-to-NSPCL 264
9.2.2.1 UseofSameLinkerandSolidSupportforSPPSandSPCL 265
9.2.2.2 Re-immobilizationoftheC-TerminalSegment 266
9.3 SPCLintheN-to-CDirection 268
9.3.1 TemporaryMaskingGroupstoEnableIterativeLigations 268
9.3.2 LinkersforN-to-CSPCL 270
9.3.3 CaseStudy 272
9.3.4 SPCLwithConcomitantPurifications 274
9.4 Post-LigationSolid-SupportedTransformations 274
9.4.1 ChemicalTransformations 274
9.4.2 BiochemicalTransformations 275
9.5 SolidSupport 275
9.6 ConclusionandPerspectives 278
Acknowledgment 278
9.A Appendix 278
References 280
10 Ser/ThrLigationforProteinChemicalSynthesis 285
CarinaHeyPuiCheungandXuechenLi
10.1 Serine/ThreonineLigation 287
10.2 EpimerizationIssue 289
10.3 OtherArylAldehydeEsters 289
10.4 PreparationofPeptideSalicylaldehydeEsters 289
10.5 ScopeandLimitations 294
10.6 StrategiesofSer/ThrLigationforProteinChemicalSynthesis 294
10.7 C-to-NSer/ThrLigation 294
10.8 N-to-CSer/ThrLigation 296
10.9 One-potSer/ThrLigationandNCL 296
10.10 Bioconjugation 296
10.11 SolubilityIssues 298
10.12 ExtensionofSer/ThrLigation 298
10.13 Conclusion 302
References 303