We have designed a new synthetic strategy for the preparation of a new class of cyclic RGD integrin ligands in which the azabicycloalkane scaffold can be envisaged as a (γ,α) dipeptide mimic. The synthesis and in vitro biological evaluation of these RGD derivatives, as well as the computational study of their conformational properties and binding modes to αVβ3 integrin are described. Compound has shown to be a promising candidate as αVβ3 integrin antagonist able to interfere with both cell adhesion and movement on vitronectin with no evidence of cytotoxic effects.

New potent alpha(v)beta(3) integrin ligands based on azabicycloalkane (gamma,alpha)-dipeptide mimics / M. Pilkington-Miksa, E.M.V. Araldi, D. Arosio, L. Belvisi, M. Civera, L. Manzoni. - In: ORGANIC & BIOMOLECULAR CHEMISTRY. - ISSN 1477-0520. - 14:12(2016), pp. 3221-3233. [10.1039/C6OB00287K]

New potent alpha(v)beta(3) integrin ligands based on azabicycloalkane (gamma,alpha)-dipeptide mimics

ARALDI, ELENA MARIA VITTORIA;L. Belvisi;M. Civera;
2016

Abstract

We have designed a new synthetic strategy for the preparation of a new class of cyclic RGD integrin ligands in which the azabicycloalkane scaffold can be envisaged as a (γ,α) dipeptide mimic. The synthesis and in vitro biological evaluation of these RGD derivatives, as well as the computational study of their conformational properties and binding modes to αVβ3 integrin are described. Compound has shown to be a promising candidate as αVβ3 integrin antagonist able to interfere with both cell adhesion and movement on vitronectin with no evidence of cytotoxic effects.
Assisted drug-delivery; biological evaluation; molecular-mechanics; binding analysis; structural basis; antagonists; proteins; design; angiogenesis; peptides
Settore CHIM/06 - Chimica Organica
Sintesi e applicazioni biomediche di peptidomimetici in campo oncologico
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/387439
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