The phosphotryptophan derivative l-Pro-l-Leu-l-(P)Trp(OH)2 (2b) was reported as the first example of left-hand-side1 phosphonate inhibitor of MMP-8. Its uncommon mode of binding to MMP-8 was mainly ascribed to the presence of the proline residue in P3. Ten new analogues of 2b were obtained by replacement of the aminoterminal l-Pro with aminoacid residues bearing small side chains. Most of the new analogues show an increase of affinity for MMP-2 and MMP-8, and different profiles of selectivity. Computer simulations were performed to explain the effects of substitutions on the preferred mode of binding. They reveal that most of the new analogues are probably accommodated in the right, rather than left-hand side of MMP-8 active site. © 2005 Elsevier SAS. All rights reserved.

Synthesis and evaluation of new tripeptide phosphonate inhibitors of MMP-8 and MMP-2 / Mariangela, Agamennone; Cristina, Campestre; Serena, Preziuso; Consalvi, Valerio; Marcello, Crucianelli; Fernando, Mazza; Vincenzo, Politi; Ragno, Rino; Paolo, Tortorella; Carlo, Gallina. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 40:3(2005), pp. 271-279. [10.1016/j.ejmech.2004.10.013]

Synthesis and evaluation of new tripeptide phosphonate inhibitors of MMP-8 and MMP-2

CONSALVI, Valerio;RAGNO, Rino;
2005

Abstract

The phosphotryptophan derivative l-Pro-l-Leu-l-(P)Trp(OH)2 (2b) was reported as the first example of left-hand-side1 phosphonate inhibitor of MMP-8. Its uncommon mode of binding to MMP-8 was mainly ascribed to the presence of the proline residue in P3. Ten new analogues of 2b were obtained by replacement of the aminoterminal l-Pro with aminoacid residues bearing small side chains. Most of the new analogues show an increase of affinity for MMP-2 and MMP-8, and different profiles of selectivity. Computer simulations were performed to explain the effects of substitutions on the preferred mode of binding. They reveal that most of the new analogues are probably accommodated in the right, rather than left-hand side of MMP-8 active site. © 2005 Elsevier SAS. All rights reserved.
2005
left-hand inhibitors; matrix metalloproteinases inhibitors; mmp; right-hand inhibitors; tripeptide phosphonates
01 Pubblicazione su rivista::01a Articolo in rivista
Synthesis and evaluation of new tripeptide phosphonate inhibitors of MMP-8 and MMP-2 / Mariangela, Agamennone; Cristina, Campestre; Serena, Preziuso; Consalvi, Valerio; Marcello, Crucianelli; Fernando, Mazza; Vincenzo, Politi; Ragno, Rino; Paolo, Tortorella; Carlo, Gallina. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 40:3(2005), pp. 271-279. [10.1016/j.ejmech.2004.10.013]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/239389
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