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Peptide ligands with restricted mobility through a Suzuki reaction: design, synthesis and evaluation

Objetivo

The aim of this research proposal is the application of the Suzuki-Miyaura reaction to the synthesis of peptidic libraries with restricted mobility. Specifically, we envision the synthesis of a family of cyclic peptides that will contain a biaryl bond, to further restrain their conformation. This biaryl bond will be obtained through a Suzuki-Miyaura set of reactions between two aromatic amino acid derivatives in the sequence. Initially, the reaction conditions will be optimized on simple models: the order in which the bicyclic peptides should be assembled, solid vs. solution-phase, Suzuki-Miyaura reaction conditions…Once the synthesis has been optimized, several peptide libraries will be prepared, progressively increasing the synthetic challenge and including D- and non-proteinogenic amino acids. The ultimate goal of the project is to obtain new series of peptides which will act as ligands of certain protein surfaces (POP, DPP-IV and VEGF), for which they will have been designed. The sequences to be synthesized will be first decided on rational design basis assisted through evolutionary algorithms and, later, based on the results obtained for the interaction with the therapeutic target. Special attention will be placed on the conformational study of such constrained molecules. The interaction of the new peptides with the proteins surfaces, as well as their ADME properties will be evaluated through different methods.

Convocatoria de propuestas

FP7-PEOPLE-2009-RG
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Coordinador

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Aportación de la UE
€ 45 000,00
Dirección
CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA
08028 Barcelona
España

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Región
Este Cataluña Barcelona
Tipo de actividad
Research Organisations
Contacto administrativo
Stel.La Serra (Ms.)
Enlaces
Coste total
Sin datos