Inactivation of boar acrosin by peptidyl-arginyl-chloromethanes. Comparison of the reactivity of acrosin, trypsin and thrombin.
A survey of the reactivity of 16 peptidyl-argininyl-chloromethanes with boar acrosin indicated that these compounds as a general group of reagents were highly effective in the inactivation of acrosin since at least half of the reagents tested rapidly inactivated this protease at a concentration of 0.10 micrometer or lower. For example, Dns-Glu-Gly-ArgCH2Cl inactivates acrosin by 50% in 1.8 min at a concentration of 75 nM, whereas in contrast, a 14000-fold higher concentration of Nalpha-tosyllysyl-chloromethane is required to obtain an equivalent rate of inactivation. A comparison of the reactivity of acrosin and trypsin with the peptides of arginyl-chloromethane containing different substituents in the P2 and P3 positions suggests that the secondary binding sites of these two proteases are very similar. Reagents with homoarginine, lysine and D-arginine in the P1 position have also been prepared and evaluated, but these were considerably less effective than the corresponding arginyl-chloromethanes in the inactivation of both acrosin and trypsin.
D000176:Acrosin / Q000037:antagonists & inhibitors*; D000345:Affinity Labels; D000590:Amino Acid Chloromethyl Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001665:Binding Sites; D007700:Kinetics; D011480:Protease Inhibitors; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D000345:Affinity Labels; D000590:Amino Acid Chloromethyl Ketones; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D001120:Arginine; D000176:Acrosin; D013917:Thrombin