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 A.; BAIULA M.; BELVISI L.; VIOLA A.; GENTILUCCI L.; TROISI S.; DATTOLI S. D.; SPAMPINATO S.; CIVERA M.; JUARISTI E.; ESCUDERO M.. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 66:(2013), pp. 258-268. [10.1016/j.ejmech.2013.05.050]
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 receptorI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
