Detail of "35909-92-3"

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1-Peptidyl-2-haloacetyl hydrazines as active site directed inhibitors of papain and cathepsin B

1-Peptidyl-2-haloacetyl hydrazines as active site directed inhibitors of papain and cathepsin B. Giordano, Cesare; Calabretta, Raffaele; Gallina, Carlo; Consalvi, Valerio; Scandurra, Roberto (Cent. Stud. Chim. Farm., Univ. Sapienza, Rome, Italy). Farmaco, 46(12), 1497-516 (English) 1991. CODEN: FRMCE8. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 7, 34 Fifteen 1-peptidyl-2-haloacetyl hydrazines, which can be considered halometanes of azapeptides contg. Phe in P2 and a-aza-Ala or a-aza-Gly in P1, were synthesized and tested as models of cysteine-proteases inhibitors. By use of kinetic methods, they proved to irreversibly inactivate papain and cathepsin B via a reversible enzyme-inhibitor intermediate. Second-order rate consts. of inactivation in the range 26-23000 M-1s-1 were obsd. for papain and 2000-39600 M-1s-1 for cathepsin B. K1 for the reversible E1 adducts ranged from 230 to 0.16 mM for papain and from 11 to 0.37 mM for cathepsin B. Structure of possible reversible E1 complex is proposed and used to discuss the effects of structural variation of the inhibitors on the kinetic parameters of inactivation. The title compds. proved to be selective for cysteine-proteases, since no inhibiting activity could be detected toward trypsin, chymotrypsin and porcine pancreatic elastase at 0.1 mM concn., after 6 h incubation.Several reagents such as 35909-92-3 is used here. Relatively low aspecific alkylating properties were also verified in tests using glutathione as the nucleophile. .