Kinetics of Hydrolysis of Phenylthiazolones of Arginine, Homoarginine, Norarginine, and Canavanine by Trypsin

抄録

Phenylthiazolones (PTAs) of arginine and its homologs and analogs, homoarginine, norarginine (α-amino-γ-guanidinobutyric acid), canavanine, and γ-hydroxyarginine, were prepared. A steady-state kinetic analysis of the trypsin [EC 3.4.21.4]-catalyzed hydrolysis reactions was carried out and the kinetic parameters for these internal thioesters were compared with those for normal linear ester substrates. PTA-γ-hydroxyarginine was so labile that hydrolysis by the enzyme could not be followed. PTA-arginine has a specificity constant (kcat/Km) com-parable to that for the N^α-unblocked arginine ester substrate, though the value is about 0.1% of that for a specific ester substrate, N^α-tosylarginine methyl ester. PTA derivatives of cana-vanine and homoarginine were hydrolyzed with kcztlKm values of the same order of magnitude as that for PTA-arginine. However, PTA-norarginine was much less susceptible to tryptic hydrolysis than PTA-homoarginine, while the linear esters of norarginine are known to be more susceptible than those of homoarginine.