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《多肽合成副反应（英文版）》是作者在十多年多肽合成第一手经验的基础之上，结合大量相关文献完成的。
内容简介
全书系统地介绍了多肽合成中最常见的副反应，其产生的机理，以及相应的解决方案。其中很多副反应的产生是在GMP生产条件下被发现并加以研究的，其形成机理与生产工艺的开发紧密相关。多肽杂质的形成对于多肽类API的GMP生产具有非常关键的影响，因此检测和分析多肽杂质对成功的API工业生产至关重要。而掌握多肽副反应产生的机理、分析手段及相应的优化方案，则是整个多肽API工艺开发和生产环节中的核心要素。
《多肽合成副反应（英文版）》可供学术界与工业界相关人员参考使用。
作者简介
作者杨翼。
章节目录
版权信息
内容简介
Preface
Chapter 1 Peptide Fragmentation/Deletion Side Reactions
1.1 ACIDOLYSIS OF PEPTIDES CONTAINING N-Ac-N-alkyl-Xaa MOTIF
1.2 Des-Ser/Thr IMPURITIES INDUCED BY O -acyl ISODIPEPTIDE Boc-Ser/Thr(Fmoc-Xaa)-OH AS BUILDING BLOCK FOR PEPTIDE SYNTHESIS
1.3 ACIDOLYSIS OF - N -acyl- N -alkyl-Aib-Xaa- BOND
1.4 ACIDOLYSIS OF -Asp-Pro- BOND
1.5 AUTODEGRADATION OF PEPTIDE N -TERMINAL H-His-Pro-Xaa- MOIETY
1.6 ACIDOLYSIS OF THE PEPTIDE C -TERMINAL N -Me-Xaa
1.7 ACIDOLYSIS OF PEPTIDES WITH N -TERMINAL FITC MODIFICATION
1.8 ACIDOLYSIS OF THIOAMIDE PEPTIDE
1.9 DEGUANIDINATION SIDE REACTION ON Arg
1.10 DKP (2,5-DIKETOPIPERAZINE) FORMATION
REFERENCES
Chapter 2 β -Elimination Side Reactions
2.1 β -ELIMINATION OF Cys SULFHYDRYL SIDE CHAIN
2.2 β -ELIMINATION OF PHOSPHORYLATED Ser/Thr
REFERENCES
Chapter 3 Peptide Global Deprotection/Scavenger-Induced Side Reactions
3.1 TERT-BUTYLATION SIDE REACTION ON Trp DURING PEPTIDE GLOBAL DEPROTECTION
3.2 Trp ALKYLATION BY RESIN LINKER CATIONS DURING PEPTIDE CLEAVAGE/GLOBAL DEPROTECTION
3.3 FORMATION OF Trp-EDT AND Trp-EDT-TFA ADDUCT IN PEPTIDE GLOBAL DEPROTECTION
3.4 Trp DIMERIZATION SIDE REACTION DURING PEPTIDE GLOBAL DEPROTECTION
3.5 Trp REDUCTION DURING PEPTIDE GLOBAL DEPROTECTION
3.6 Cys ALKYLATION DURING PEPTIDE GLOBAL DEPROTECTION
3.7 FORMATION OF Cys-EDT ADDUCTS IN PEPTIDE GLOBAL DEPROTECTION REACTION
3.8 PEPTIDE SULFONATION IN SIDE CHAIN GLOBAL DEPROTECTION REACTION
3.9 PREMATURE Acm CLEAVAGE OFF Cys(Acm) AND Acm S→ O MIGRATION DURING PEPTIDE GLOBAL DEPROTECTION
3.10 METHIONINE ALKYLATION DURING PEPTIDE SIDE CHAIN GLOBAL DEPROTECTION WITH DODT AS SCAVENGER
3.11 THIOANISOLE-INDUCED SIDE REACTIONS IN PEPTIDE SIDE CHAIN GLOBAL DEPROTECTION
REFERENCES
Chapter 4 Peptide Rearrangement Side Reactions
4.1 ACID CATALYZED ACYL N → O MIGRATION AND THE SUBSEQUENT PEPTIDE ACIDOLYSIS
4.2 BASE CATALYZED ACYL O → N MIGRATION
4.3 His-Nim-INDUCED ACYL MIGRATION
REFERENCES
Chapter 5 Side Reactions Upon Amino Acid/Peptide Carboxyl Activation
5.1 FORMATION OF N -ACYLUREA UPON PEPTIDE/AMINO ACID-CARBOXYL ACTIVATION BY DIC
5.2 URONIUM/GUANIDINIUM SALT COUPLING REAGENTS-INDUCED AMINO GROUP GUANIDINATION SIDE REACTIONS
5.3 δ -LACTAM FORMATION UPON Arg ACTIVATION REACTION
5.4 NCA FORMATION UPON Boc/Z-AMINO ACID ACTIVATION
5.5 DEHYDRATION OF SIDE CHAIN-UNPROTECTED Asn/Gln DURING CARBOXYL-ACTIVATION
5.6 FORMATION OF H- β -Ala-OSu FROM HOSu-CARBODIIMIDE REACTION DURING AMINO ACID CARBOXYL-ACTIVATION
5.7 BENZOTRIAZINONE RING OPENING AND PEPTIDE CHAIN TERMINATION DURING CARBODIIMIDE/HOOBt MEDIATED COUPLING REACTIONS
5.8 PEPTIDE CHAIN TERMINATION THROUGH THE FORMATION OF PEPTIDE N -TERMINAL UREA IN CDI-MEDIATED COUPLING REACTION
5.9 GUANIDINO OR HYDANTOIN-2-IMIDE FORMATION FROM CARBODIIMIDE AND Nα GROUP ON AMINO ACID/PEPTIDE
5.10 SIDE REACTIONS-INDUCED BY CURTIUS REARRANGEMENT ON PEPTIDE ACYL AZIDE
5.11 FORMATION OF PYRROLIDINAMIDE-INDUCED BY PYRROLIDINE IMPURITIES IN PHOSPHONIUM SALT
REFERENCES
Chapter 6 Intramolecular Cyclization Side Reactions
6.1 ASPARTIMIDE FORMATION
6.1.1 Factors That Infl uence Aspartimide Formation
6.1.2 Solutions for Aspartimide Formation
6.2 Asn/Gln DEAMIDATION AND OTHER RELEVANT SIDE REACTIONS
6.2.1 Mechanism of Asn/Gln Deamidation
6.2.2 Factors Impacting on Asn/Gln Deamidation
6.2.3 Infl uences of Asn/Gln Deamidation on Peptide Chemical Synthesis
6.3 PYROGLUTAMATE FORMATION
6.4 HYDANTOIN FORMATION
6.5 SIDE REACTIONS ON N -TERMINAL Cys(Cam) AND N -BROMOACETYLATED PEPTIDE
REFERENCES
Chapter 7 Side Reactions on Amino Groups in Peptide Synthesis
7.1 N α-ACETYLATION SIDE REACTIONS
7.2 TRIFLUOROACETYLATION SIDE REACTIONS
7.3 FORMYLATION SIDE REACTIONS
7.3.1 Trp(For)-Induced Peptide Formylation
7.3.2 Formic Acid-Induced Peptide Formylation
7.3.3 DMF-Induced Peptide Formylation
7.4 PEPTIDE N -ALKYLATION SIDE REACTIONS
7.4.1 Chloromethyl Resin Induced Peptide N -Alkylation Side Reactions
7.4.2 Peptide N -Alkylation During Deblocking of N α-Urethane Protecting Group
7.4.3 Peptide N -Alkylation During Global Deprotection
7.4.4 N -Alkylation Side Reaction on N -Terminal His via Acetone-Mediated Enamination
7.5 SIDE REACTIONS DURING AMINO ACID Nα-PROTECTION(Fmoc-OSu INDUCED Fmoc-β -Ala-OH AND Fmoc- β -Ala-AA-OH DIPEPTIDE FORMATION)
REFERENCES
Chapter 8 Side Reactions on Hydroxyl and Carboxyl Groups in Peptide Synthesis
8.1 SIDE REACTIONS ON Asp/Glu SIDE CHAIN AND PEPTIDE BACKBONE CARBOXYLATE
8.1.1 Base-Catalyzed Asp/Glu(OBzl) Transesterifi cation Side Reaction During the Loading of Chloromethyl Resin
8.1.2 Esterifi cation Side Reactions on Asp/Glu During Peptidyl Resin Cleavage and Product Purifi cation
8.2 SIDE REACTIONS ON Ser/Thr SIDE CHAIN HYDROXYL GROUPS
8.2.1 Alkylation Side Reactions on Ser/Thr Side Chain Hydroxyl Groups
8.2.2 Acylation Side Reactions on Ser/Thr Side Chain Hydroxyl Groups
8.2.3 β -Elimination Side Reactions on Ser/Thr
8.2.4 N -Terminal Ser/Thr-Induced Oxazolidone Formation Side Reactions
8.2.5 Ser/Thr-Induced Retro Aldol Cleavage Side Reaction
REFERENCES
Chapter 9 Peptide Oxidation/Reduction Side Reactions
9.1 OXIDATION SIDE REACTIONS ON Cys
9.2 OXIDATION SIDE REACTIONS ON Met
9.3 OXIDATION SIDE REACTIONS ON Trp
9.4 OXIDATION SIDE REACTIONS ON OTHER AMINO ACIDS AND AT NONSYNTHETIC STEPS
9.5 PEPTIDE REDUCTION SIDE REACTIONS
REFERENCES
Chapter 10 Redundant Amino Acid Coupling Side Reactions
10.1 DIPEPTIDE FORMATION DURING AMINO ACID Nα-Fmoc DERIVATIZATION
10.2 REDUNDANT AMINO ACID COUPLING VIA PREMATURE Fmoc DEPROTECTION
10.2.1 Lys- N ε-Induced Fmoc Premature Cleavage
10.2.2 N α-Proline-Induced Fmoc Premature Cleavage
10.2.3 DMF/NMP-Induced Fmoc Premature Cleavage
10.2.4 Residual Piperidine-Induced Fmoc Premature Cleavage
10.2.5 DMAP/DIEA-Induced Fmoc Premature Cleavage
10.2.6 Hydrogenation-Induced Fmoc Premature Cleavage
10.2.7 Fmoc Deblocking in the Starting Material
10.3 REDUNDANT AMINO ACID COUPLING INDUCED BY NCA FORMATION
10.4 His- N imPROMOTED Gly REDUNDANT INCORPORATION
10.5 REDUNDANT COUPLING INDUCED BY THE UNDESIRED AMINO ACID-CTC RESIN CLEAVAGE
10.6 REDUNDANT AMINO ACID COUPLING INDUCED BY INSUFFICIENT RESIN RINSING
10.7 REDUNDANT AMINO ACID COUPLING INDUCED BY OVERACYLATION SIDE REACTION
REFERENCES
Chapter 11 Peptide Racemization
11.1 PEPTIDE RACEMIZATION MECHANISM
11.1.1 Peptide Racemization via Oxazol-5(4 H )-one Formation
11.1.2 Peptide Racemization via Enolate Formation
11.1.3 Peptide Racemization via Direct H αAbstraction
11.1.4 Peptide Racemization via Aspartimide Formation
11.1.5 Acid-Catalyzed Peptide Racemization
11.2 RACEMIZATION IN PEPTIDE SYNTHESIS
11.2.1 Amino Acids with a High Tendency of Racemization in Peptide Synthesis
11.2.2 DMAP-Induced Racemization
11.2.3 Microwave Irradiation-Induced Racemization
11.2.4 Racemization During Peptide Segment Condensation
11.3 STRATEGIES TO SUPPRESS RACEMIZATION IN PEPTIDE SYNTHESIS
11.3.1 Amino Acid N α-Protecting Group
11.3.2 Amino Acid Side Chain Protecting Group
11.3.3 Coupling Reagent
11.3.4 Coupling Tactics
11.3.5 Solvent
11.3.6 Base
11.3.7 Amino Acid Activation Mode
11.3.8 Temperature
11.3.9 Cu(II) Salt Additive
REFERENCES
Chapter 12 Side Reactions in Peptide Phosphorylation
12.1 FORMATION OF H -PHOSPHONATE SIDE PRODUCT
12.2 FORMATION OF PYROPHOSPHATE SIDE PRODUCT
REFERENCES
Chapter 13 Cys Disulfide-Related Side Reactions in Peptide Synthesis
13.1 DISULFIDE SCRAMBLING VIA THIOL-DISULFIDE EXCHANGE
13.2 DISULFIDE DEGRADATION AND CONSEQUENT TRISULFIDE AND LANTHIONINE FORMATION
13.2.1 Disulfi de Degradation Pattern
13.2.2 Trisulfi de Formation
13.2.3 Lanthionine Formation
REFERENCES
Chapter 14 Solvent-Induced Side Reactions in Peptide Synthesis
14.1 DCM-INDUCED SIDE REACTION
14.2 DMF-INDUCED SIDE REACTION
14.2.1 DMF-Induced N -Formylpiperidine Formation
14.2.2 DMF-Induced Formylation Side Reactions
14.2.3 DMF-Induced Acid Chloride Formation Side Reactions
14.3 METHANOL/ETHANOL-INDUCED SIDE REACTIONS
14.3.1 Methanol-Induced Esterifi cation Side Reactions
14.3.2 Methanol-Induced N -Alkylation Side Reactions in Catalytic Hydrogenation
14.4 ACETONITRILE-INDUCED SIDE REACTION
14.5 ACETONE-INDUCED SIDE REACTION
14.6 MTBE-INDUCED SIDE REACTION
14.7 TFE-INDUCED SIDE REACTION
REFERENCES
Appendix I Molecular Weight Deviation of Peptide Impurity
REFERENCE
Appendix II List of Abbreviations
Subject Index
SideReactionsinPeptideSynthesis多肽合成副反应是2015年由清华大学出版社出版,作者杨翼。
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