Structure-inhibitory activity relationship of plasmin and plasma kallikrein inhibitors

Based on the structure of Tra-Tyr(O-Pic)-octylamide, a portion of the octyl amine was replaced with moieties bearing hydrophobic, basic or acidic group s. Replacement of the C-terminal residue with a moiety bearing a hydrophobi c 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 t he affinity of the inhibitor, a carboxylic acid attached to the phenyl ring increased the PK selectivity of the inhibitor.