A HEPARIN-BINDING SYNTHETIC PEPTIDE OF HEPARIN HEPARAN SULFATE-INTERACTING PROTEIN MODULATES BLOOD-COAGULATION ACTIVITIES/

We have previously identified and characterized a heparin-binding cell surface protein (heparin/heparan sulfate-interacting protein, or HIP) present on epithelial and endothelial cells. A synthetic peptide mimi cking a heparin-binding domain of HIP is now shown to bind a small sub set of heparin molecules with high affinity and, therefore, presumably recognizes a specific structural motif in the heparin molecule, Furth er analyses revealed that the heparin molecules exhibiting a high affi nity for the HIP peptide also show an extremely high affinity for anti thrombin III (AT-III), a cofactor required for heparin's anticoagulant activity, The HIP peptide was shown to compete with AT-III for bindin g to heparin and to neutralize the anticoagulant activity of heparin i n blood plasma assays, Furthermore, the heparin subfraction that binds to the HIP peptide with high affinity exhibits an extremely high anti coagulant activity. We conclude that although the HIP peptide shows no sequence similarity with AT-III, the two proteins recognize the same or similar structural motifs in heparin.