Structure-inhibitory activity relationship of plasmin and plasma kallikrein inhibitors.
Based on the structure of Tra-Tyr(O-Pic)-octylamide, a portion of the octylamine was replaced with moieties bearing hydrophobic, basic or acidic groups. Replacement of the C-terminal residue with a moiety bearing a hydrophobic group gave the proper affinity of the inhibitor to both plasmin (PL) and plasma kallikrein (PK). While addition of a basic residue did not improve the affinity of the inhibitor, a carboxylic acid attached to the phenyl ring increased the PK selectivity of the inhibitor.
Tsuda
Y
Y
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan.
Tada
M
M
Wanaka
K
K
Okamoto
U
U
Hijikata-Okunomiya
A
A
Okamoto
S
S
Okad
Y
Y
D000588:Amines / Q000737:chemistry; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005341:Fibrinolysin / Q000737:chemistry*; D005342:Fibrinolysis; D006801:Humans; D020842:Plasma Kallikrein / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000737:chemistry; D014357:Trypsin / Q000737:chemistry; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry
D000588:Amines; D004791:Enzyme Inhibitors; D020842:Plasma Kallikrein; D014357:Trypsin; D013917:Thrombin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; C008699:octylamine