Novel RGD-like molecules based on the tyrosine template: design, synthesis, and biological evaluation on isolated integrins alphaVbeta3/alphaIIbbeta3 and in cellular adhesion tests

Bioorganic & Medicinal Chemistry
Stéphane BiltresseJacqueline Marchand-Brynaert

Abstract

RGD (Arg-Gly-Asp) peptidomimetics have been designed for covalent anchorage on biomaterials. The tyrosine template was thus equipped with (i) a basic side chain of various flexibility, (ii) an acidic side chain, which incorporated the XPS fluorine tag, and (iii) a spacer-arm terminated by a primary amine for surface grafting. The most active compounds showed IC50 values in the nanomolar range versus isolated human integrins alphaVbeta3 and alphaIIbbeta3. Preincubation of CaCo2 cells with soluble peptidomimetics (2 and 19a) prevented cellular adhesion on culture plates coated with vitronectin. On the other hand, peptidomimetics (19a and 19b) immobilized on a poly(ethylene)terephthalate membrane (PET) promoted CaCo2 cells adhesion. A modeling study at the ab initio level in MINI-1' basis allowed to compare the various synthetic ligands of integrins and to propose novel pharmacophore structures.

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Citations

Mar 16, 2013·Bioorganic & Medicinal Chemistry·Sri Kamesh NarasimhanYan-Yeung Luk
Jun 7, 2005·Bioorganic & Medicinal Chemistry Letters·Sabrina DevougeJacqueline Marchand-Brynaert
Sep 1, 2005·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Brian C Monk, David R K Harding
Feb 22, 2005·Biomaterials·Stéphane BiltresseJacqueline Marchand-Brynaert
May 5, 2009·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Virginie FievezVéronique Préat
Jun 4, 2016·Angewandte Chemie·Carlos Mas-MorunoHorst Kessler
May 16, 2008·Chembiochem : a European Journal of Chemical Biology·Dominik HeckmannHorst Kessler
Nov 19, 2005·Organic & Biomolecular Chemistry·Claudio SalvagniniJacqueline Marchand-Brynaert
Oct 29, 2009·Journal of Medicinal Chemistry·Vincent ReratJacqueline Marchand-Brynaert
Dec 25, 2007·Bioorganic & Medicinal Chemistry Letters·Maryam MomtazJacqueline Marchand-Brynaert

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