Mutations within the reactive-site region of human pancreatic secretory trypsin inhibitor confer α-thrombin and factor xa inhibitory activities

Abstract

Mutations were introduced into the reactive-site region of human pancreatic secretory trypsin inhibitor (PSTI) to produce thrombin and/or factor Xa inhibitors. All of five mutants showed trypsin inhibitory activity as strong as wild-type PSTI. Moreover, the Arg (P1), Pro-Arg (P2-P1), and Pro-Arg-Ile-Tyr-Asn (P2-P1-P1-P2′-P3′) (bold letters indicate replaced amino acids compared to the wild type) mutants had additional inhibitory activities toward factor Xa, both thrombin and factor Xa, and thrombin, respectively, at 1×10−5 m. © 1997, Taylor & Francis Group, LLC. All rights reserved.