title: Inhibition of adamalysin II and MMPs by phosphonate analogues of snake venom peptides.
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.
authors.affiliation: Polifarma Research Center, Roma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: D'Alessio
authors.forename: C
authors.initials: C
authors.lastname: Gallina
authors.forename: E
authors.initials: E
authors.lastname: Gavuzzo
authors.forename: C
authors.initials: C
authors.lastname: Giordano
authors.forename: B
authors.initials: B
authors.lastname: Gorini
authors.forename: F
authors.initials: F
authors.lastname: Mazza
authors.forename: M P
authors.initials: MP
authors.lastname: Paradisi
authors.forename: G
authors.initials: G
authors.lastname: Panini
authors.forename: G
authors.initials: G
authors.lastname: Pochetti
authors.forename: A
authors.initials: A
authors.lastname: Sella
mesh_terms: D020128:Inhibitory Concentration 50; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008956:Models, Chemical; D012910:Snake Venoms / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013696:Temperature
chemical_list: D012910:Snake Venoms; D008666:Metalloendopeptidases; C028220:Crotalus adamanteus proteinase II