Peptide synthesis soluble polymeric reagents

Peptide Synthesis Using Soluble Polymeric Reagents... 

Thus, in this method the stepwise synthesis proceeds on the soluble polymer, as in the liquid phase method the only difference is in the coupling step where the carboxyl component is an insoluble polymeric active ester. The use of the solubilizing C-terminal macromolecular protecting group overcomes the limitations encountered in the original application of the polymer reagent method of peptide synthesis. However, due to the steric limitations characteristic of the polymer-polymer interactions, the attainment of quantitative coupling in each step of the synthesis can be difficult in this method. 

Unlike reagents bound to crosslinked polymeric supports, soluble macromolecules are able to interact with reactive groups attached to insoluble polymers. This fact was demonstrated by Frank and Hagenmaier, who developed an alternating liquid-solid phase peptide synthesis procedure. Amino acids attached to crosslinked polystyrene via a carbamate linker were condensed with a peptide ester of polyethyleneglycol monostearylether (Scheme 1.6.12). 

The use of insoluble polymeric carriers has greatly simplified the synthesis of peptides purification of the growing peptide chain in the repetitive steps is achieved by filtration procedures that simply remove all soluble reagents and byproducts from the reaction medium, whilst the covalently resin-hnked macromolecule is retained on the insoluble polymeric support. In all sohd-phase reactions of this type, the polymeric support represents the medium on or in which the chemical reaction takes place. Correspondingly, this medium is represented by the total amount of insoluble polymer present, which in the case of polymeric beads is divided into small, individual reaction compartments. Resin parameters such as the degree of crosshnking, the polarity of the resin, its sweUing properties, mass-transport, phase transitions, bead size, and the particle size distribution therefore have to be taken into serious consideration. 

The principal difference between the synthesis of individual peptides and peptide libraries is that mixtures of amino acids, rather than individual amino acids, are incorporated into selected or all positions of the sequence of peptide libraries. However, all current peptide chemistry strategies can be used for the synthesis of peptide libraries. In general, library synthesis requires greater emphasis on simplicity and reproducibility of the synthesis process. Although soluble supports have also been used for peptide library synthesis,the majority of methods used to synthesize peptide combinatorial libraries utilize Merrifield s concept of solid-phase synthesis,which is based on the sequential assembly of peptides after covalent attachment of the C-terminal amino acid to a polymeric solid support. This enables the excess of reagents to be removed by simple wash and filtration processes, and avoids the... 

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