Methods for the Chemical Synthesis and Readout of Self-Encoded Arrays of Polypeptide Analogues

Abstract

The synthesis of defined arrays of polypeptide analogues in conjunction with a simple self-encoded chemical readout system provides a powerful method for the systematic investigation of the relationship between polypeptide molecular structure and function. A novel solid-phase synthesis procedure was used to prepare arrays of polypeptide analogues in which a specific modification was systematically incorporated into a unique position in a peptide sequence. The synthesis was carried out in such a way that the resulting arrays contained a defined family of modified peptides, with each peptide molecule containing only a single specific modification. The array of polypeptide analogues was self-encoded in a positional fashion by incorporating a selectively cleavable bond into the analogue structure. Following cleavage of the polypeptide analogue array, analysis of the resulting peptide fragments by MALDI mass spectrometry defined, in a single step, the presence and identity of each peptide analogue in the mixtu...