Table Of ContentChemoselectiveand
BioorthogonalLigationReactions
Chemoselective and
Bioorthogonal Ligation Reactions
ConceptsandApplications
Editedby
W.RussAlgar,PhilipE.DawsonandIgorL.Medintz
Volume1
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v
ContentstoVolume1
ListofContributors xi
Preface xvii
PartI Chemistries 1
1 ABriefIntroductiontoTraditionalBioconjugateChemistry 3
W.RussAlgar
1.1 Introduction 3
1.2 ReactiveGroupsofBiomolecules 3
1.2.1 PeptidesandProteins 4
1.2.2 Carbohydrates 7
1.2.3 NucleicAcids 10
1.2.4 Lipids 12
1.3 TraditionalBioconjugateReactions 13
1.3.1 AminesandOtherNitrogenReagents 14
1.3.1.1 AldehydesandKetones 15
1.3.1.2 ActiveEstersofAcids 15
1.3.1.3 Isothiocyanates 17
1.3.1.4 OtherReactiveGroups 17
1.3.2 Thiols 18
1.3.2.1 Maleimides 18
1.3.2.2 AlkylHalidesandHaloacetamides 19
1.3.2.3 ActivatedDisulfides 19
1.3.3 HydroxylsandPhenols 20
1.4 Cross-LinkingStrategies 21
1.4.1 Zero-LengthCross-LinkingorTracelessLigations 21
1.4.2 HomobifunctionalandHeterobifunctionalLinkers 22
1.4.3 FunctionalGroupConversion 24
1.4.4 Biotin–Avidin 25
1.5 ChallengesAssociatedwithTraditionalBioconjugate
Reactions 27
1.6 Conclusions 30
References 30
vi Contents
2 [3+2]-DipolarCycloadditionsinBioconjugation 37
JasonE.Hein
2.1 Introduction 37
2.2 Copper-CatalyzedStrategies 38
2.2.1 Cu(I)-CatalyzedAzide–AlkyneCycloaddition(CuAAC) 38
2.2.1.1 Introduction 38
2.2.1.2 Mechanism 40
2.2.1.3 Benefits,Limitations,andApplications 42
2.2.1.4 Summary 46
2.2.2 ClickSulfonamideReaction(CSR) 47
2.2.2.1 Introduction 47
2.2.2.2 Mechanism 48
2.2.2.3 Benefits,Limitations,andApplications 49
2.2.2.4 Summary 50
2.3 Strain-PromotedCycloaddition 50
2.3.1 Strain-PromotedAzide–AlkyneCycloaddition(SPAAC) 50
2.3.1.1 Introduction 50
2.3.1.2 Mechanism 51
2.3.1.3 Benefits,Limitations,andApplications 54
2.3.1.4 Summary 57
2.3.2 Strain-PromotedCycloadditionwithOtherDipoles 57
2.3.2.1 Introduction 57
2.3.2.2 Mechanism 57
2.3.2.3 Benefits,Limitations,andApplications 57
2.3.2.4 Summary 60
2.4 FutureDirections 60
References 61
3 Diels–AlderandInverseDiels–AlderReactions 67
RobertoJ.BreaandNealK.Devaraj
3.1 Introduction 67
3.2 Diels–AlderReaction 67
3.2.1 ChemicalAspects 68
3.2.1.1 Mechanism 68
3.2.1.2 Reactivity 68
3.2.1.3 MolecularOrbitals 69
3.2.2 Precursors 70
3.2.2.1 Electron-RichDienes 70
3.2.2.2 Electron-DeficientDienophiles 70
3.2.3 KeyFeatures 70
3.2.3.1 FastReactionRates 70
3.2.3.2 Chemoselectivity,Regioselectivity,andStereoselectivity 71
3.2.4 Applications 72
3.2.4.1 ProteinLabelingandImmobilization 72
3.2.4.2 Peptide–OligonucleotideConjugation 75
3.3 InverseDiels–AlderReaction 76
3.3.1 ChemicalAspects 77
Contents vii
3.3.1.1 Mechanism 77
3.3.1.2 Reactivity 78
3.3.1.3 MolecularOrbitals 79
3.3.2 Precursors 80
3.3.2.1 Electron-DeficientDienes:Tetrazines 80
3.3.2.2 Electron-RichDienophiles 81
3.3.3 KeyFeatures 83
3.3.3.1 FastKinetics 83
3.3.3.2 Bioorthogonality 84
3.3.3.3 MutualOrthogonalitywithOther“Click”Reactions 84
3.3.4 Applications 85
3.3.4.1 RadiolabeledBiomarkers 85
3.3.4.2 PretargetedProbesforInVivoandInVitroImaging 86
3.3.4.3 DNA/RNAModificationandGeneticEncoding 87
3.4 SummaryandOutlook 89
References 89
4 TheStaudingerLigation 97
OlaiaNieto-García,MarcieB.Jaffee,MichaelaMühlberg,and
ChristianP.R.Hackenberger
4.1 MechanismandScopeoftheClassicalStaudingerReaction 97
4.2 MethodologyandMechanismoftheNontracelessStaudinger
Ligation 99
4.3 MethodologyandMechanismoftheTracelessStaudinger
Ligation 100
4.4 MethodologyandMechanismoftheStaudinger-Phosphiteand
Staudinger-PhosphoniteReaction 104
4.5 ApplicationsoftheStaudingerLigationanditsVariantsas
BioorthogonalTools 107
4.5.1 StaudingerLigationandTracelessStaudingerLigation 107
4.5.2 Staudinger-PhosphiteReaction 109
References 111
5 Thiol–EneChemistry 117
NeilB.CramerandChristopherN.Bowman
5.1 Introduction 117
5.2 MechanismandStereochemistry 119
5.2.1 Thiol-Michael 120
5.2.2 Thiol–Ene 122
5.2.2.1 Initiation 122
5.2.2.2 Propagation 124
5.2.2.3 Termination 125
5.2.2.4 Thiol–Yne 125
5.3 ReactionKinetics 127
5.4 ChemoselectivityandSideReactions 129
5.4.1 ReactionwithOxygen 129
5.4.2 OdorandShelfStability 131
viii Contents
5.5 ApplicationsandRepresentativeExamplesfromtheLiterature 132
5.5.1 HomogeneousNetworks 133
5.5.2 ShrinkageStressandDentalMaterials 134
5.5.3 PolymerFunctionalization,SurfaceGrafting,andBioconjugation 135
5.5.4 PolymerCross-linking 136
5.5.5 HydrogelsandDrugDelivery 136
References 137
6 Ligand-DirectedTosylandAcylImidazoleChemistry 147
KazuyaMatsuoandItaruHamachi
6.1 Introduction 147
6.1.1 AffinityLabelingofNaturalProteins 148
6.1.2 Ligand-DirectedChemistryforOne-StepTracelessLabeling 150
6.2 Ligand-DirectedTosylChemistry 150
6.2.1 FundamentalPropertiesofLDTChemistryInVitro 150
6.2.2 ApplicationsofLDTChemistry 153
6.3 Ligand-DirectedAcylImidazoleChemistry 155
6.3.1 FundamentalPropertiesofLDAIChemistryInVitro 156
6.3.2 ApplicationsofLDAIChemistry 158
6.4 ConclusionsandFutureDirections 160
References 160
7 BioorthogonalLabelingofCellularProteinsbyEnzymaticand
RelatedMechanisms 165
ScottA.Walper,KendrickB.Turner,andIgorL.Medintz
7.1 Introduction 165
7.2 EnzymaticLabeling 166
7.2.1 BiotinLigase 166
7.2.2 Farnesyltransferase 170
7.2.3 Formylglycine-GeneratingEnzyme 172
7.2.4 LipoicAcidLigase 174
7.2.5 Peroxidase 177
7.2.6 PhosphopantetheinylTransferase 179
7.2.7 Sortase 181
7.2.8 Transglutaminase 185
7.3 Self-LabelingProteinsandPeptides 190
7.3.1 SNAP/CLIP-Tags 190
7.3.2 HaloTag 195
7.3.3 Activity-BasedProteinProfiling 199
7.4 AlternateMethodsofProteinLabeling 201
7.4.1 BiarsenicalDyes 201
7.4.2 SpyCatcher/SpyTag 203
7.4.3 SplitInteins 206
7.4.4 SplitProteins 208
7.5 Conclusions 211
Acknowledgments 211
References 211
Contents ix
8 Metal-MediatedBioconjugation 231
JustinM.Chalker
8.1 SelectiveBondFormationonBiomoleculesUsing
Organometallics 231
8.2 OxidativeLigationsatTyrosine(Ni,Pd,Ru,Ce) 232
8.3 Indium-MediatedLigations 235
8.4 ReductiveAlkylationofLysine(Ir) 237
8.5 Metal-PromotedCysteineAlkylation(Au,Rh) 237
8.6 LigationsFeaturingRhodiumCarbenoids 241
8.7 Tsuji–TrostAlkylationofTyrosine(Pd) 244
8.8 Mizoroki–HeckReaction(Pd) 245
8.9 Cross-CouplingatAlkynes(Pd,Cu) 247
8.10 Suzuki–MiyauraCross-Coupling(Pd) 251
8.11 OlefinMetathesis(Ru) 254
8.12 ProspectsinMetal-MediatedLigations 257
References 258
ContentstoVolume2
ListofContributors xiii
Preface xix
PartII Applications 271
9 ProteinandAntibodyLabeling 273
AngelaM.MarianiandKimE.Sapsford
10 Activity-BasedProteinProfiling 305
ElianeV.WolfandStevenH.L.Verhelst
11 NucleicAcidLabeling,Ligation,andModification 335
AfafH.El-SagheerandTomBrown
12 ChemoselectiveReactionsforGlycanLabeling 363
JanetE.McCombsandJenniferJ.Kohler
13 ChemoselectiveAttachmentofLipidstoProteins 391
ChristianF.W.Becker
14 InVivoApplicationsofBioorthogonalChemistries 417
ChelseaG.GordonandCarolynR.Bertozzi
15 ImmobilizationofBiomolecularProbesforArraysandAssay:
CriticalAspectsofBiointerfaces 459
StellaH.NorthandChrisRoweTaitt
x Contents
16 ChemicalLigationsintheDesignofHydrogelMaterials 497
ScottH.MedinaandJoelP.Schneider
17 NanoparticleBioconjugates:MaterialsthatBenefitfrom
ChemoselectiveandBioorthogonalLigationChemistries 543
MelissaMasseyandW.RussAlgar
18 ApplicationofEngineeredViralNanoparticlesinMaterials
andMedicine 631
MichaelD.GliddenII,JohnF.Edelbrock,AmyM.Wen,SourabhShukla,
YingfangMa,RogerH.French,JonathanK.Pokorski,andNicoleF.Steinmetz
Index 711
v
ContentstoVolume1
ListofContributors xi
Preface xvii
PartI Chemistries 1
1 ABriefIntroductiontoTraditionalBioconjugateChemistry 3
W.RussAlgar
2 [3+2]-DipolarCycloadditionsinBioconjugation 37
JasonE.Hein
3 Diels–AlderandInverseDiels–AlderReactions 67
RobertoJ.BreaandNealK.Devaraj
4 TheStaudingerLigation 97
OlaiaNieto-García,MarcieB.Jaffee,MichaelaMühlberg,andChristianP.R.
Hackenberger
5 Thiol–EneChemistry 117
NeilB.CramerandChristopherN.Bowman
6 Ligand-DirectedTosylandAcylImidazoleChemistry 147
KazuyaMatsuoandItaruHamachi
7 BioorthogonalLabelingofCellularProteinsbyEnzymaticand
RelatedMechanisms 165
ScottA.Walper,KendrickB.Turner,andIgorL.Medintz
8 Metal-MediatedBioconjugation 231
JustinM.Chalker
