Two c[RGDfX] cyclopeptides, having either L- or D-morpholine-3-COOH (Mor) as the X amino acid were developed as ligands for alpha(v)beta(3)/alpha(v)beta(5) integrins. Biological assays showed only d-Mor-containing cyclopentapeptide capable to bind alpha(v)beta(3) integrin with a low nanomolar affinity according to a two-site model, thus revealing a connection between the configuration of Mor and the preferred binding to alpha(v)beta(3) integrin. Conformational analysis showed different structural preferences for the two peptides induced by the two enantiomeric cyclic amino acids, suggesting a role of the stereochemistry of Mor on the overall peptide conformation and on the presentation of the pharmacophoric Arg and Asp side chains.

Morpholine-based RGD-cyclopentapeptides as alphavbeta3/alphavbeta5 integrin ligands: role of configuration towards receptor binding affinity / N. Cini;A. Trabocchi;G. Menchi;A. Bottoncetti;S. Raspanti;A. Pupi;A. Guarna. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 17:(2009), pp. 1542-1549. [10.1016/j.bmc.2009.01.006]

Morpholine-based RGD-cyclopentapeptides as alphavbeta3/alphavbeta5 integrin ligands: role of configuration towards receptor binding affinity.

CINI, NICOLETTA;TRABOCCHI, ANDREA;MENCHI, GLORIA;BOTTONCETTI, ANNA;RASPANTI, SILVIA;PUPI, ALBERTO;GUARNA, ANTONIO
2009

Abstract

Two c[RGDfX] cyclopeptides, having either L- or D-morpholine-3-COOH (Mor) as the X amino acid were developed as ligands for alpha(v)beta(3)/alpha(v)beta(5) integrins. Biological assays showed only d-Mor-containing cyclopentapeptide capable to bind alpha(v)beta(3) integrin with a low nanomolar affinity according to a two-site model, thus revealing a connection between the configuration of Mor and the preferred binding to alpha(v)beta(3) integrin. Conformational analysis showed different structural preferences for the two peptides induced by the two enantiomeric cyclic amino acids, suggesting a role of the stereochemistry of Mor on the overall peptide conformation and on the presentation of the pharmacophoric Arg and Asp side chains.
2009
17
1542
1549
N. Cini;A. Trabocchi;G. Menchi;A. Bottoncetti;S. Raspanti;A. Pupi;A. Guarna
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/628471
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