Inhibition studies of some serine and thiol proteinases by new leupeptin analogues.
Fifteen tripeptide analogues of leupeptin containing either a C-terminal argininal or lysinal were synthesized. The synthetic analogues were tested, using spectrophotometric assay techniques, as inhibitors of trypsin, kallikrein, thrombin, plasmin, and cathepsin B. The lysinal analogues were fairly selective as inhibitors of cathepsin B activity. Acetyl-L-leucyl-L-valyl-L-lysinal (21) showed a stronger inhibition of cathepsin B (IC50 = 4 nanomolar) than leupeptin. Acetyl-L-phenylalanyl-L-valyl-L-argininal (2i) was found to be a good inhibitor of cathepsin B (IC50 = 0.039 microM), thrombin (IC50 = 1.8 microM), and plasmin (IC50 = 2.2 microM).
McConnell
R M
RM
University of Arkansas, Monticello 71655.
York
J L
JL
Frizzell
D
D
Ezell
C
C
D000595:Amino Acid Sequence; D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D002417:Cattle; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007976:Leupeptins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D002401:Cathepsin B