Solid-phase peptide synthesis SPPS

The Merrifield school has also designed linkers that permit peptides to be detached by different methods (Tam et al., 1981). A linker based on the benzhydry- 

It is most important to avoid the formation of byproducts during the coupling reactions. Syntheses using unsymmetrical anhydrides that might cleave in the wrong 

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Redox-sensitive resin 24 designed for solid-phase peptide synthesis (SPPS) [29] was prepared from commercially available 2,5-dimethylben-zoquinone in seven steps [30] and loaded to a support via a Wittig reaction. Release of the peptide occurs using two sequential mild conditions, reduction with NaBH4 followed by TBAF-catalyzed cyclic ether formation (Scheme 8) which provide orthogonality to acid sensitive reactions. 

Work in the Imperiali laboratory has also focused on exploring the ability of minimal peptide scaffolds to augment the rate of coenzyme-mediated transaminations [22-25]. To accomplish this, a strategy has been developed in which the core functionality of the coenzyme is incorporated as an integral constituent of an unnatural coenzyme amino acid chimera construct. Thus, non-cova-lent binding of the coenzyme to the peptide or protein scaffold is unnecessary. Both the pyridoxal and pyridoxamine analogs have been synthesized in a form competent for Fmoc-based solid phase peptide synthesis (SPPS) (Fig. 7) [23,24]. 

The first version of solid-phase peptide synthesis (SPPS) to be developed used the /-Boc group as the amino-protecting group. It can be cleaved with relatively mild acidic treatment, and TFA is usually used. The original coupling reagent was dicyclohexylcar-... 

In preparing these various libraries, extensive use is made of solid phase synthetic methods. These methods are all derived from the solid phase peptide synthesis (SPPS) method developed by Merrifield in 1963. When performing a large number of syntheses, it is preferable to perform the synthetic steps on a solid bead rather than completing the entire synthesis in the solution phase. The solid-phase technique makes byproduct removal and final compound purification easier. The organic chemistry literature contains a wealth of different types of solid-phase supports and novel linkers for attaching the synthetic substrate to the bead. 

PolyHIPE has found a successful application in the field of solid phase peptide synthesis (SPPS), where the highly porous microstructure acts as a support material for a polyamide gel [134]. The polystyrene matrix is functionalised to give vinyl groups on its internal surfaces, and is then impregnated with a DMF solution of N, JV -dimethylacrylamide, acryloylsarcosine methyl ester, crosslinker and initiator. Polymerisation grafts the soft gel onto the rigid support, giving a novel composite material (Fig. 16). 

Since the first systematic synthetic effort of Leplawy et al)22 the preparation of peptides containing the slow-reacting C -tetrasubstituted a-amino acids has been achieved mainly by solution procedures. However, recent improvements in activation methodologies make solid-phase peptide synthesis (SPPS) an attractive tool as well, at least with the less sterically hindered Ca-tetrasubstituted a-amino acids. 

Fig. 3 General scheme for solid-phase peptide synthesis (SPPS)...

The purpose of this chapter is to delineate strategic considerations and provide practical procedures to enable non-experts to synthesize peptides with a reasonable chance of success. This chapter focuses on Fmoc chemistry, which is now the most commonly employed strategy for solid phase peptide synthesis (SPPS). Protocols for the synthesis of fully deprotected peptides are presented, together with a review of linkers and supports currently employed for SPPS. The principles and the different steps of SPPS (anchoring, deprotection, coupling reaction, and cleavage) are all discussed, along with their possible side reactions. 

This chapter provides a manual for a laboratory-hased short course to introduce the common techniques of solid-phase peptide synthesis (SPPS). The course provides students the opportunity to design and manually synthesize analogs of glutathione using relatively simple equipment available in any unsophisticated laboratory. The manual provides compact protocols for both the different steps of SPPS and the final cleavage of peptides from resin supports. We also introduce a simple method for the synthesis of combinatorial libraries of glutathione analogs that is suitable for those relatively unfamiliar with the field of peptide chemistry. 

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