抄録
The reason for the difference between the binding mechanisms of an anti-thrombosis drug, Argatroban ((2R, 4R)-4-methyl-1-[N2-((RS)-3-methyl-1, 2, 3, 4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidine carboxylic acid, MQPA), and bovine basic pancreatic trypsin inhibitor ( BPTI) was clarified by X-ray crystallographic analysis of MQP-trypsin complex: The difference is not due to the carboxyl group in Argatroban, but is attributed to the total conformation of the inhibitor. The binding mechanism explains the specificities of a series of Argatroban-related inhibitors against serine proteases. The binding structure of an anti-pancreatitis drug, Nafamostat, to trypsin unexpectedly showed that the amidinonaphthalene portion was inserted into the specificity pocket. Another anti-pancreatitis drug, Camostat, was found to bind covalently to trypsin. These results provide bases for novel drug design strategies.
