title: Inhibition of human leukocyte elastase by N-substituted tripeptide trifluoromethyl ketones.
abstract: 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.
authors.affiliation: Department of Biochemistry, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877.
authors.forename: J W
authors.initials: JW
authors.lastname: Skiles
authors.forename: V
authors.initials: V
authors.lastname: Fuchs
authors.forename: G
authors.initials: G
authors.lastname: Chow
authors.forename: M
authors.initials: M
authors.lastname: Skoog
mesh_terms: 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
chemical_list: D007659:Ketones; D009842:Oligopeptides; D010196:Pancreatic Elastase