Author/Authors :
Silvana D’Alessio، نويسنده , , Carlo Gallina، نويسنده , , Enrico Gavuzzo، نويسنده , , Cesare Giordano، نويسنده , , Barbara Gorini، نويسنده , , Fernando Mazza، نويسنده , , Mario Paglialunga Paradisi، نويسنده , , Gabriella Panini، نويسنده , , Giorgio Pochetti، نويسنده , , Antonio Sella، نويسنده ,
Abstract :
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)2 showed 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. ©
