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