Combinatorial library screening coupled to mass spectrometry to identify valuable cyclic peptides

SILVIA A. CAMPERI; SILVANA L. GIUDICESSI; MARÍA C. MARTÍNEZ CERON; JUAN M. GUREVICH-MESSINA; SOLEDAD L. SAAVEDRA; GERARDO ACOSTA; OSVALDO CASCONE; ROSA ERRA BALSELLS; FERNANDO ALBERICIO

Curr Protoc Chem Biol

Wiley

Año: 2016 vol. 8 p. 109 - 130

2160-4762

Combinatorial library screening coupled to mass spectrometry (MS) analysis has proven to be a practical approach to identify useful peptides. Cyclic peptides usually have high biological activity, selectivity and affinity for target proteins and strong stability against proteolytic degradation. Here we describe two strategies to prepare combinatorial libraries suitable for MS analysis to accelerate the discovery of cyclic peptides structures. In both approaches ChemMatrix resin and the linker 4-hydroxymethylbenzoic acid is used. In one strategy, a one-bead-two-peptides library in which each bead contains both the cyclic peptide and its linear counterpart, facilitates MS analysis. The other protocol is based on the synthesis of a cyclic depsipeptide library in which a glycolamidic ester group is incorporated by adding glycolic acid. After library screening, ring is opened and peptide is released simultaneously for subsequent MS analysis.