Methods and compositions related to mutant kunitz domain i of tfpi-2

Abstract

Disclosed are methods and compositions relating to plasmin inhibition.

What is claimed is: 
     
         1 . A polypeptide comprising the amino acid sequence set forth in SEQ ID NO:1 or a sequence having at least 79% identity with SEQ ID NO:1, with a leucine to arginine, serine, threonine, asparagine, histidine or lysine substitution at position 17, using BPTI numbering system; wherein the polypeptide inhibits plasmin activity and has decreased anticoagulation activity as compared to a wild type KDI polypeptide. 
     
     
         2 . The polypeptide of  claim 1 , wherein the amino acid sequence has at least 80% identity to SEQ ID NO:1. 
     
     
         3 . The polypeptide of  claim 1 , wherein the amino acid sequence has at least 81% identity to SEQ ID NO:1. 
     
     
         4 . The polypeptide of  claim 1 , wherein the amino acid sequence has at least 82% identity to SEQ ID NO:1. 
     
     
         5 . The polypeptide of  claim 2 , which comprises a tyrosine to glutamic acid substitution at position 46. 
     
     
         6 . The polypeptide of  claim 1 , which comprises a tyrosine to threonine substitution at position 11. 
     
     
         7 . The polypeptide of  claim 1 , which comprises an aspartic acid to tyrosine substitution at position 10. 
     
     
         8 . The polypeptide of  claim 1 , which comprises an aspartic acid to glutamic acid substitution at position 10. 
     
     
         9 . The polypeptide of  claim 1 , which comprises an alanine to methionine, glycine or serine substitution at position 16. 
     
     
         10 . The polypeptide of  claim 1 , which comprises a leucine to arginine substitution at position 17. 
     
     
         11 . The polypeptide of  claim 10 , which comprises a tyrosine to threonine substitution at position 11. 
     
     
         12 . The polypeptide of  claim 1 , which comprises one or more mutations selected from the group consisting of: a tyrosine to threonine substitution at position 11, an alanine to methionine, glycine, or serine substitution at position 16, and an aspartic acid to tyrosine or glutamic acid substitution at position 10. 
     
     
         13 . A composition comprising the polypeptide of  claim 1 . 
     
     
         14 . A nucleic acid encoding the polypeptide of  claim 1 .