Inhibition of human leukocyte elastase by N-substituted tripeptide trifluoromethyl ketones.
Several tripeptide trifluoromethyl ketones containing non-naturally occurring N-substituted glycine residues at the P2-position are effective human leukocyte elastase (HLE) inhibitors in vitro and possess IC50 values in the submicromolar range. Deletion of the amino acid at the P3-subsite region affords inactive compounds. The trifluoromethyl ketone derivative of valine is the preferred residue at the P1-position; whereas, the corresponding glycine or alpha, alpha-dimethyl glycine analogs result in inactive compounds.
Skiles
J W
JW
Department of Biochemistry, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877.
Fuchs
V
V
Chow
G
G
Skoog
M
M
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D066298:In Vitro Techniques; D007659:Ketones / Q000494:pharmacology*; D007962:Leukocytes / Q000201:enzymology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D007659:Ketones; D009842:Oligopeptides; D010196:Pancreatic Elastase