Matrix-assisted laser desorption ionization for rapid determination of the sequences of biologically active peptides isolated from support-bound combinatorial peptide libraries.

A termination synthesis approach has been developed to encode each resin bead in support-bound combinatorial peptide libraries with the information needed to establish the sequence of the full-length products also contained on the beads. Matrix-assisted laser desorption ionization mass spectrometry was then used to rapidly read the appropriate sequences. In addition to rapid peptide sequencing, the technique allows direct assessment of the quality of the synthetic library, since deletion peptides, side-reaction products and incomplete-deprotection products are readily observed. An anti-gp120 monoclonal antibody was screened against a hexapeptide library, and eight active peptides were isolated. Six of the eight peptides were shown to possess the exact recognition sequence for the antibody.