Friendly strategy to prepare encoded one bead-one compound cyclic peptide library

GIUDICESSI, S. L.; GUREVICH-MESSINA, J M; MARTÍNEZ CERON, MARÍA C.; ERRA BALSELLS, R.; ALBERICIO, F.; CASCONE, O.; CAMPERI, S A

ACS Paragon Plus Environment, ACS Combinatorial Science

ACS Publications

Año: 2013 vol. 15 p. 525 - 529

2156-8952

One-bead-one-peptide libraries allow the screening of suitable ligands for any target protein. Short cyclic peptides are ideal ligands for affinity chromatography due to their high affinity and selectivity for the target protein and stability against proteases. We designed a library synthesis strategy to facilitate the identification of cyclic peptides by MS consisting in: a) sequential incorporation of a mixture of Fmoc-Ala-OH and Fmoc-Asp[2-phenylisopropyl (OPp)]-OH (15:85) to Gly-oxymethylbenzamide-ChemMatrix (Gly-HMBA-CM) resin, b) synthesis of the combinatorial library on the resin by the divide-couple-recombine method, c) removal of OPp with 4% TFA, d) peptide cyclization on solid phase through side-chain Asp and amino terminus, e) removal of side chain protecting groups with a 95% TFA cocktail. Peptides were cleaved from the beads with ammonia and the linear code was sequenced by MALDI-TOF MS/MS. The high capacity of ChemMatrix resin together with the sensitivity of MS allows code sequencing from a single bead.