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., et al. (2013). Modulation of αvβ3- and α5β1-integrin-mediated adhesion by dehydro-β-amino acids containing peptidomimetics. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 66, 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.
