Solid-phase synthesis of polypeptides

Over the past decade the techniques of combinatorial synthesis have received much attention. Solid phase synthesis of polypeptides and oligonucleotides are especially adaptable to combinatorial synthesis, but the method is not limited to these fields. The goal of combinatorial synthesis is to prepare a large number of related... 

The success of solid-phase synthesis of polypeptides has stimulated efforts to use polymer substrates in other biochemical and organic syntheses ... 

Likewise, in the preparation of many ion-exchange resins, suitable functional groups are introduced by secondary reactions of macromolecular substances (that are generally crosslinked see Sect. 5.2). In this context the utilization of crosslinked polystyrene resins or poly(acrylamide) gel in the solid-phase synthesis of polypeptides (Merrifield technique) or even oligonucleotides should be mentioned. After complete preparation of the desired products they are cleaved from the crosslinked substrate and can be isolated. 

Other polymeric substrates, such as poly(N,N-dimethylacrylamide) and graft polymers derived from hydroxyl group containing crosslinked polystyrene and ethylene oxide are also nsed as solid phases. In the latter example diisopropylcarbodiimide is used in the coupling reaction. Also, diisopropylcarbodiimide/HOBt is used in the solid phase synthesis of polypeptides. Ammonium salts derived from polymer bound N-hydroxysuccinimide are also used in the EDC mediated amidation reaction. ... 

Several reports published within the year describe new photocleavage protecting groups. The accounts by Misetic and Boyd, and Giegrich et al. outline such mechanisms for primary alcohols and in nucleoside/nucleotide systems respectively, while the work of Akerblom et al. is relevant to the synthesis of combinatorial chemical libraries on solid phases and that of McGall et al. is of use in the solid phase synthesis of polypeptides and oligonucleotides. 

Combinatorial chemistry is a sophisticated set of techniques used to synthesize, pnrify, analyze, and screen large numbers of chemical compounds, far faster and cheaper than was previously possible. The direct precursor of combinatorial chemistry was the solid-phase synthesis of polypeptides developed by American biochemist Robert Bruce Merrifield in the 1960s, followed by the advances in laboratory automation since then. Initial development of the field has been led by the pharmaceutical industry in the search for new drugs, but its applications are spreading into other fields of chemistry. Other terms associated with this field are parallel array synthesis and high-throughput chemistry. 

Solid Phase Synthesis of Polypeptides. A reaction sequence has been designed for the solid-phase synthesis of a polypeptide esterified at the C-terminus with the phenol functionality in 4-hydroxy-6-mercaptodibenzofuran and resin bound with a disulfide bond (eq 4). There are certain liabilities associated with the method (the lability of the disulfide bond, that of the phenyl ester, cyclization with formation of diketopiperazides after the amine is liberated in the second chain elongation step, etc.). A detailed protocol has been designed to circumvent these issues. i... 

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