Modulation of αvβ3- and α5β1-integrin-mediated adhesion by dehydro-β-amino acids containing peptidomimetics
Articolo
Data di Pubblicazione:
2013
Citazione:
Modulation of αvβ3- and α5β1-integrin-mediated adhesion by dehydro-β-amino acids containing peptidomimetics / A. Tolomelli, M. Baiula, L. Belvisi, A. Viola, L. Gentilucci, S. Troisi, S.D. Dattoli, S. Spampinato, M. Civera, E. Juaristi, M. Escudero. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 66(2013), pp. 258-268.
Abstract:
A novel class of low molecular weight ligands of αvβ 3 and α5β1 integrins, that possess a dehydro-&beta-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 con firmed that the dehydro-β-amino derivatives are able to act as an electrostatic clamp by establishing several stabilizing interactions with the receptor.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Dehydro-β-amino acids ; Peptidomimetic ; Cell adhesion ; Signaling ; Drug discovery
Elenco autori:
A. Tolomelli, M. Baiula, L. Belvisi, A. Viola, L. Gentilucci, S. Troisi, S.D. Dattoli, S. Spampinato, M. Civera, E. Juaristi, M. Escudero
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