9780199637249

Fmoc Solid Phase Peptide Synthesis A Practical Approach

by ;
  • ISBN13:

    9780199637249

  • ISBN10:

    0199637245

  • Edition: 1st
  • Format: Paperback
  • Copyright: 2000-03-02
  • Publisher: Oxford University Press

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Summary

In the years since the publication of Atherton and Sheppard's volume, the technique of Fmoc solid-phase peptide synthesis has matured considerably and is now the standard approach for the routine production of peptides. The basic problems outstanding at the time of publication of this earlier work have now been, for the most part, solved. As a result, innovators in the field have focussed their efforts to develop methodologies and chemistry for the synthesis of more complex structures. The focus of this new volume is much broader, and covers not only the essential procedures for the production of linear peptides but also more advanced techniques for preparing cyclic, side-chain modified, phospho- and glycopeptides. Many other methods also deserving attention have been included: convergent peptide synthesis; peptide-protein conjugation; chemoselective ligation; and chemoselective purification. The difficult preparation of cysteine and methionine-containing peptides is also covered, as well as methods for overcoming aggregation during peptide chain assembly and a survey of available automated instrumentation.

Table of Contents

List of Contributors
xvii
Abbreviations xxi
Introduction---a retrospective viewpoint
1(8)
R. C. Sheppard
Basic principles
9(32)
Peter D. White
Weng C. Chan
The solid phase principle
9(2)
Merrifield SPPS
11(1)
Fmoc/tBu SPPS
11(30)
Resins
13(2)
Linkers
15(11)
Side-chain protecting groups
26(1)
First residue attachment
26(1)
Coupling step
27(1)
N-Fmoc deprotection reaction
27(3)
Aggregation
30(1)
Enantiomerization
31(1)
Side reactions
32(4)
Cleavage reaction
36(1)
Limitations
36(1)
References
37(4)
Basic procedures
41(36)
Weng C. Chan
Peter D. White
Introduction
41(1)
Manual synthesis
41(1)
Resin handling
41(3)
Resin functionalization
44(1)
Attachment of the first residue
44(7)
Hydroxymethyl-based resins
44(6)
Trityl-based linkers
50(1)
Aminomethyl-based linkers
51(1)
Fmoc removal
51(1)
Coupling methods
52(8)
DIC/HOBt
53(1)
Active esters
54(1)
Symmetrical anhydride
55(2)
Aminium/phosphonium activation methods
57(2)
Acid fluorides
59(1)
Assembly of the peptide chain
60(1)
Analytical procedures
61(3)
Resin tests
61(1)
Bromophenol blue monitoring
62(1)
Fmoc determination
62(1)
HPLC analysis
63(1)
TFA-mediated cleavage
64(13)
Preparing the resin for cleavage
64(1)
Cleavage reactions releasing fully deprotected peptides
65(5)
Peptide isolation
70(2)
Monitoring the cleavage reaction
72(1)
Release of fully protected peptides from hyper-acid labile supports with 1% TFA
73(1)
References
74(3)
Preparation and handling of peptides containing methionine and cysteine
77(38)
Fernando Albericio
Ioana Annis
Mirian Royo
George Barany
Introduction
77(1)
Methionine
78(3)
Cysteine
81(34)
Cysteine protection
81(6)
Solid phase synthesis of cysteine-containing peptides
87(4)
Formation of disulphides
91(18)
References
109(6)
Difficult peptides
115(22)
Martin Quibell
Tony Johnson
Introduction
115(1)
Difficult peptides--an overview
115(4)
Background
115(2)
Identifying the effects of aggregation
117(1)
Effect of resins, solvents, and additives on aggregation
118(1)
Predicting difficult peptide sequences
119(3)
The N-(2-hydroxy-4-methoxybenzyl) (Hmb) backbone amide protecting group
122(15)
Development and preparation of (Hmb) amino acid derivatives
122(3)
Incorporation of N-(2-hydroxy-4-methoxybenzyl)amino acid residues
125(2)
Site selection for Hmb back bone protection
127(1)
Improved difficult peptide syntheses through Hmb backbone protection
128(3)
Use of Hmb protection to increase solution solubility
131(1)
References
132(5)
Synthesis of modified peptides
137(46)
Sarah L. Mellor
Donald A. Wellings
Jean-Alain Fehrentz
Marielle Paris
Jean Martinez
Nicholas J. Ede
Andrew M. Bray
David J. Evans
G. B. Bloomberg
C-terminal modifications
137(29)
Peptidyl N-alkyl amides
137(4)
Use of the 4-hydroxymethylbenzoic acid linkage agent for the synthesis of C-terminal modified peptides
141(8)
Peptide hydroxamic acids
149(4)
Peptide aldehydes by solid phase synthesis
153(8)
Synthesis of C-terminal peptide aldehydes on the Multipin™ system using the oxazolidine linker
161(5)
N-terminal modifications
166(3)
Biotinylation
167(1)
Reductive alkylation
168(1)
Side-chain modifications
169(14)
Introduction
169(1)
Strategy design in the synthesis of atypical peptides
169(9)
References
178(5)
Phosphopeptide synthesis
183(12)
Peter D. White
Introduction
183(1)
Building block approach
183(4)
Introduction
183(1)
Practical considerations
184(1)
Illustrative examples
185(2)
Global phosphorylation
187(5)
Introduction
187(2)
General protocol for post-synthetic phosphorylation
189(1)
Illustrative examples
190(1)
Thiophosphorylated peptides
191(1)
Analysis of phosphopetides
192(3)
HPLC analysis
192(1)
Mass spectroscopy
192(1)
References
193(2)
Glycopeptide synthesis
195(20)
Jan Kihlberg
Introduction
195(2)
Strategic considerations in glycopeptide synthesis
197(1)
Formation of glycosidic linkages to amino acids
198(2)
Choosing protective groups for glycosylated amino acids
200(3)
Protection of the α-amino group
200(1)
Protection of the α-carboxyl group
201(1)
Protection of the carbohydrate hydroxyl groups
201(1)
Suitable linkers and resins
202(1)
Preparation of glycosylated amino acids
203(6)
Synthesis of a glycopetide from HIV gp120
209(6)
References
211(4)
Convergent peptide synthesis
215(14)
Kleomenis Barlos
Dimitrios Gatos
Introduction
215(1)
Strategy in convergent synthesis
215(1)
Solid phase synthesis of protected peptide fragments
216(4)
Fragment selection
216(1)
Synthesis of protected peptide fragments
216(4)
Solid phase fragment condensation
220(3)
Esterification of the C-terminal fragment on 2-chlorotrityl chloride resin
220(1)
Activation and condensation of protected peptide fragments
221(2)
Phase and direction change
223(4)
Fragment condensation in solution
223(2)
Two-directional synthesis. Attachment of fragments on resins of the trityl-type through an amino acid side chain functional group
225(2)
Deprotection, purification, and purity determination of the synthetic peptides
227(2)
References
227(2)
Methods of preparing peptide---carrier conjugates
229(14)
Jan W. Drijfhout
Peter Hoogerhout
Introduction
229(1)
Homobifunctional cross-linking
229(2)
Heterobifunctional cross-linking
231(5)
Conjugation of thiol-containing peptides to proteins
231(3)
Conjugation of peptides to thiolated carriers
234(2)
MAP-core constructs as peptide-carriers
236(7)
Sequential synthesis of MAPs
237(1)
Synthesis of MAPs by fragment condensation
237(2)
References
239(4)
Chemoselective and orthogonal ligation techniques
243(22)
James P. Tam
Y.-A. Lu
Introduction
243(1)
Chemoselective non-amide ligation
244(8)
Thiol chemistry
245(2)
Carbonyl chemistry
247(5)
Orthogonal amide ligation
252(13)
Carbonyl chemistry
252(6)
Thiol chemistry
258(4)
References
262(3)
Purification of large peptides using chemoselective tags
265(12)
Paolo Mascagni
Introduction
265(1)
Purification of large polypeptides using Fmoc-based chromatographic probes
266(2)
The concept of selective and reversible labelling
266(2)
Capping of unreacted polypeptide chains in SPPS
268(1)
RP-HPLC using lipophilic chromatographic probes
269(5)
Affinity chromatography using biotinylated chromatographic probes
274(3)
References
276(1)
Instrumentation for automated solid phase peptide synthesis
277(26)
Linda E. Cammish
Steven A. Kates
Introduction
277(2)
Batchwise peptide synthesis
279(8)
PE Biosystems Model 433A peptide synthesis system
280(3)
Protein Technologies, Inc., SONATA/Pilot™ peptide synthesizer
283(1)
Protein Technologies Inc., Model PS3™ peptide synthesizer
283(1)
Advanced ChemTech Model 90 peptide synthesizer
284(2)
Advanced ChemTech Model 400 production-scale synthesizer
286(1)
ABIMED EPS 221 synthesizer
287(1)
Continuous-flow peptide synthesis
287(4)
PE Biosystems Pioneer™ peptide synthesis system
289(2)
Multiple peptide synthesis systems
291(8)
PE Biosystems Pioneer MPS option
291(1)
Protein Technologies, Inc., SYMPHONY/Multiplex™ peptide synthesizer
292(1)
Advanced ChemTech Models 348, 396, and 357 bimolecular synthesizers
293(1)
ABIMED AMS 422 multiple peptide synthesizer
294(2)
ABIMED ASP 222 Auto-Spot Robot
296(1)
ZINSSER ANALYTIC SMPS 350 multiple peptide synthesizer
297(1)
ZINSSER ANALYTIC SOPHAS solid phase synthesizer
298(1)
SHIMADZU PSSM-8 peptide synthesizer
298(1)
Conclusions
299(4)
References
300(3)
Manual multiple synthesis methods
303(26)
B. Dorner
J. M. Ostresh
R. A. Houghten
Ronald Frank
Andrea Tiepold
John E. Fox
Andrew M. Bray
Nicholas J. Ede
Ian W. James
Geoffrey Wickham
Simultaneous multiple peptide synthesis---the T-bag method
303(2)
Introduction
303(1)
The T-bag method
303(2)
Multiple peptide synthesis with the SPOT-technique
305(9)
Introduction
305(3)
Synthesis of peptide SPOT-arrays
308(5)
Applications of peptide SPOT-arrays
313(1)
Manual multipeptide synthesis in block arrays
314(5)
Hardware
314(1)
Chemistry
315(2)
Software
317(2)
Synthesis of peptides by the Multipin™ method
319(10)
Introduction
319(1)
Linkers
320(1)
Peptide synthesis
321(4)
References
325(4)
Appendices 329(12)
A1 Equipment and reagents for peptide synthesis
329(2)
A2 List of suppliers
331(6)
A3 Useful tables
337(4)
Index 341

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