Document Report Card

Basic Information

ID: ALA2417442

Journal: Eur J Med Chem

Title: Modulation of αvβ₃- and α₅β₁-integrin-mediated adhesion by dehydro-β-amino acids containing peptidomimetics.

Authors: Tolomelli A, Baiula M, Belvisi L, Viola A, Gentilucci L, Troisi S, Dattoli SD, Spampinato S, Civera M, Juaristi E, Escudero M.

Abstract: A novel class of low molecular weight ligands of αvβ₃ and α₅β₁ integrins, that possess a dehydro-β-amino acid as conformationally constrained core, linked to the pharmacophoric moieties mimicking the RGD recognition sequence, have been synthesized through a very simple protocol. Cell adhesion assays and integrin-mediated signaling activation experiments suggested a good affinity of these compounds toward both integrin receptors. Moreover, further elongation with two glycine units allowed to obtain an excellent dual inhibitor. Structural models for αvβ₃ integrin-ligand binding confirmed that the dehydro-β-amino derivatives are able to act as an electrostatic clamp by establishing several stabilizing interactions with the receptor.

CiteXplore: 23811088

DOI: 10.1016/j.ejmech.2013.05.050