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 res in bead in support-bound combinatorial peptide libraries with the info rmation needed to establish the sequence of the full-length products a lso contained on the beads. Matrix-assisted laser desorption ionizatio n mass spectrometry was then used to rapidly read the appropriate sequ ences. In addition to rapid peptide sequencing, the technique allows d irect assessment of the quality of the synthetic library, since deleti on peptides, side-reaction products and incomplete-deprotection produc ts are readily observed. An anti-gp120 monoclonal antibody was screene d against a hexapeptide library, and eight active peptides were isolat ed. Six of the eight peptides were shown to possess the exact recognit ion sequence for the antibody.