A novel class of low molecular weight ligands of alpha(v)beta(3) and alpha(5)beta(1) 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 alpha(v)beta(3) integrin-ligand binding confirmed that the dehydro-beta-amino derivatives are able to act as an electrostatic clamp by establishing several stabilizing interactions with the receptor

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

TOLOMELLI, ALESSANDRA;BAIULA, MONICA;VIOLA, ANGELO;GENTILUCCI, LUCA;TROISI, STEFANO;DATTOLI, SAMANTHA DEIANIRA;SPAMPINATO, SANTI MARIO;
2013

Abstract

A novel class of low molecular weight ligands of alpha(v)beta(3) and alpha(5)beta(1) 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 alpha(v)beta(3) integrin-ligand binding confirmed that the dehydro-beta-amino derivatives are able to act as an electrostatic clamp by establishing several stabilizing interactions with the receptor
TOLOMELLI A.; BAIULA M.; BELVISI L.; VIOLA A.; GENTILUCCI L.; TROISI S.; DATTOLI S. D.; SPAMPINATO S.; CIVERA M.; JUARISTI E.; ESCUDERO M.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/189153
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