Inhibition of Adamalysin II and MMPs by Phosphonate Analogues of Snake Venom Peptides

Autor: D’Alessio, Silvana, Gallina, Carlo, Gavuzzo, Enrico, Giordano, Cesare, Gorini, Barbara, Mazza, Fernando, Paglialunga Paradisi, Mario, Panini, Gabriella, Pochetti, Giorgio, Sella, Antonio
Zdroj: Bioorganic & Medicinal Chemistry; February 1999, Vol. 7 Issue: 2 p389-394, 6p
Abstrakt: Phosphonate analogues of the peptidomimetic N-(Furan-2-yl)carbonyl-Leu-Trp-OH were prepared with the goal of evaluating the effect of phosphonate for carboxylate replacement on binding with snake venom metalloproteinases and MMPs. N-(Furan-2-yl)carbonyl-Leu-l-Trp(P)-(OH)2showed a 75-fold increase of the inhibiting activity against adamalysin II, a snake venom metalloproteinase structurally related to MMPs and TACE. Both the phosphonate and carboxylate peptidomimetics fit into the active site adopting a retrobinding mode and provide the structural base for a new class of metalloproteinases inhibitors. ©
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