Heparin/heparan sulfate-dependent inhibitors of activated protein C and uses thereof in treating hemophilic disorders

摘要

Methods for inhibiting activated protein C (APC) comprising contacting the APC with a Kunitz polypeptide in an amount effective in inhibiting the activity of APC, wherein the Kunitz polypeptide comprises six cysteine residues at positions corresponding to positions 7, 16, 32, 40, 53, and 57 in SEQ ID NO:1, a motif X1GX2CBX′ at positions corresponding to positions 13-18 in SEQ ID NO:1, wherein each of X1 and X2, independently, is any amino acid residue, B is a basic amino acid residue, and X′ is G, A, or V; and at least one heparin-binding motif, which can present at the C-terminus of the Kunitz polypeptide.

主权项

1. A method for inhibiting activated protein C (APC), comprising contacting the APC with a Kunitz polypeptide in an amount effective in inhibiting the activity of APC,wherein:
the Kunitz polypeptide comprises the amino acid sequence of SEQ ID NO:1.