Article
Directed evolution towards protease-resistant hirudin variants.
Molecular genetics and metabolism - 1 Dec 2003
Wirsching Frank, Keller Martina, Hildmann Christian, Riester Daniel, Schwienhorst Andreas
Abstract excerpt
Hirudin, a thrombin-specific inhibitor, is efficiently digested and inactivated by proteases with pepsin- and chymotrypsin-like specificity. Using a combination of phage display selection and high-throughput screening methods, several variants of recombinant hirudin were generated. Only very few variants comprising amino acid substitutions in the amino-terminal domain (residues 1-5) and in the carboxyl-terminal...
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