Efficient Synthesis of a β-Peptide Combinatorial Library with Microwave Irradiation.

The predictable relationship between β-amino acid sequence and folding has inspired several biological applications of β-peptides. For many such applications, it would be desirable to prepare and screen β-peptide libraries. However, standard peptide synthesis protocols are not efficient enough to support a library approach for many types of β-peptides. We recently optimized the solid-phase synthesis of β-peptides using microwave irradiation, and we have now adapted this approach to synthesis on polystyrene macrobeads. We rapidly prepared a high-quality β-peptide combinatorial library via a split-and-mix strategy. This library was screened in search of β-peptide antagonists of the p53-MDM2 protein—protein interaction. [ABSTRACT FROM AUTHOR]