Inhibition of Achromobacter protease I by lysinal derivatives.
Z-Val-, Z-Pro-, Z-Leu-Leu-, and Z-Leu-Pro-lysinals and BZ-DL-lysinal were chemically synthesized and tested as novel inhibitors for Achromobacter protease I (API), a lysine-specific serine protease. Among the lysinal derivatives tested, Z-Val-lysinal was the most potent competitive inhibitor, its Ki being estimated as 6.5 nM in an esterolytic assay with Tos-Lys-OMe. In an amidolytic assay, Z-Leu-Leu-lysinal was the most potent inhibitor and the apparent mode of inhibition was non-competitive. The Kis of the other lysinal derivatives in both esterolytic and amidolytic assays were more than 10(3) times lower than that of leupeptin. Z-Val-lysinol, lacking the aldehyde group, was a poor competitive inhibitor. These results suggest that acyl-, acylaminoacyl-, and acylpeptidyllysinals function as a transition-state inhibitor for Achromobacter protease I.
Masaki
T
T
Department of Agricultural Chemistry, Faculty of Agriculture, Ibaraki University, Japan.
Tanaka
T
T
Tsunasawa
S
S
Sakiyama
F
F
Soejima
M
M
D000421:Alcaligenes / Q000201:enzymology*; D000595:Amino Acid Sequence; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects*
D009842:Oligopeptides; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; C036813:lysyl endopeptidase; D008239:Lysine