INVESTIGADORES
CAMPERI Silvia Andrea
congresos y reuniones científicas
Título:
Strategy for synthesizing cyclic peptide libraries with a minimum proportion of coding tags for mass spectrometry identification
Autor/es:
S. L. GIUDICESSI; J. M. GUREVICH-MESSINA; M. C. MARTÍNEZ-CERON; R. ERRA-BALSELLS; F. ALBERICIO; O. CASCONE; S. A. CAMPERI
Lugar:
Cayo Santa María
Reunión:
Simposio; Simposio internacional de Química; 2013
Institución organizadora:
Sociedad Cubana de Química
Resumen:
Divede-couple-recombine (DCR) method allows obtaining a library with all posible combinations of the aminoacids in the form of one bead-one peptide. 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-Glu[2-phenylisopropyl (OPp)]-OH (1:9) to Gly-hydroximethylbenzoyl (HMBA)-ChemMatrix resin (CM), b) synthesis of the combinatorial library on the resin by the DCR method, c) removal of OPp with 4% TFA, d) peptide cyclization on solid phase through side-chain Glu and amino terminus, e) removal of side chain protecting group with 95% TFA cocktail, f) library screening, h) linear code sequencing by MALDI-TOF MS/MS. The small proportion of the code (non-cycled Ala containing peptide) in comparison to the cyclic peptide avoids false positives due to the interaction of the linear peptides with the target. The high capacity of CM together with the sensitivity of MS allows code sequencing from a single bead.
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