An efficient strategy for the preparation of one-bead-one-peptide libraries on a new biocompatible solid support

A new strategy for the preparation of one-bead-one-peptide libraries compatible with solid-phase screening and subsequent detachment of the peptide from the resin for sequence determination by mass spectrometry is described. The method is based on the use of ChemMatrix, a novel, totally PEG-based resin, together with 4-hydroxymethylbenzoic acid linker. After peptide elongation, which was carried out using the Fmoc/t-Bu approach, the side-chain protecting groups were removed with TFA solution. The library was then screened, and peptides were detached from the positive beads with ammonia/THF vapor. Finally, the peptide sequences were determined by MS/MS.