STRATEGY FOR THE PREPARATION OF ONE-BEAD-ONE-CYCLIC DEPSIPEPTIDE LIBRARIES THAT CAN BE EASILY OPEN FOR ITS SEQUENCING BY MATRIX ASSISTED LASER DESORPTION/IONISATION MASS SPECTROMETRY

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

Los Cocos, Córdoba

Congreso; II Congreso Argentino de Espectrometría de Masa; 2014

Sociedad Argentina de Espectrometría de Masa

Short cyclic peptides have a great interest in therapeutic, diagnostic and affinity chromatography applications. One-bead-one-peptide libraries combined with mass spectrometry allow the screening and identification of suitable ligands for any target protein. Although linear peptides can be readily sequenced by MS, cyclic peptides typically yield complex product ion mass spectra. Here we propose a simple protocol for combinatorial cyclic libraries synthesis and ring opening before MS analysis. The protocol consisted in: a) incorporation of Fmoc-Asp[2-phenylisopropyl (OPp)]-OH to Ala-Gly-oxymethylbenzamide-ChemMatrix, b) synthesis of the combinatorial library, c) assembly of a glycolamidic ester, d) couple of an Ala residue in the N-terminal, e) removal of OPp, f) peptide cyclisation through side-chain Asp and N-Ala amino terminus, g) removal of side chain protecting groups, d) vapour phase aminolysis to simultaneously open of the ring and release the peptide and e) mass spectrometry MSMS analysis. High quality mass spectra were obtained. Peptide signals were high and their sequences could be deduced from the tandem mass spectra of each single bead evaluated. The strategy herein proposed is suitable for the preparation of one-bead-one-cyclic depsipeptide libraries that can be easily open for its sequencing by MALDI MS. It employs techniques and reagents frequently used in a broad range of laboratories without special expertise in organic synthesis.