A new method for the preparation of unprotected peptides on biocompatible resins with application in combinatorial chemistry.

[formula: see text] A synthetic strategy for the preparation of side chain free peptides on biocompatible solid supports is described. Final peptide detachment is afforded in mild basic conditions with no presence of scavengers or other additives, thus allowing single peptide-resin beads to be cleaved in mass spectrometry sample plates for direct sequencing using MALDI-TOF post-source decay. This methodology offers clear advantages for the development of one-bead--one-compound combinatorial libraries in addition to parallel and regular synthesis of peptides.