ANCYLOSTOMA-CANINUM ANTICOAGULANT PEPTIDE - A HOOKWORM-DERIVED INHIBITOR OF HUMAN COAGULATION-FACTOR XA

Human hookworm infection is a major cause of gastrointestinal blood lo ss and iron deficiency anemia, affecting up to one billion people in t he developing world, These soil-transmitted helminths cause blood loss during attachment to the intestinal mucosa by lacerating capillaries and ingesting extravasated blood. We have isolated the major anticoagu lant used by adult worms to facilitate feeding and exacerbate intestin al blood loss. This 8.7-kDa peptide, named the Ancylostoma caninum ant icoagulant peptide (AcAP), was purified by using a combination of ion- exchange chromatography, gel-filtration chromatography, and reverse-ph ase HPLC. N-terminal sequencing of AcAP reveals no homology to any pre viously identified anticoagulant or protease inhibitor, Single-stage c hromogenic assays reveal that AcAP is a highly potent and specific inh ibitor of human coagulation, with an intrinsic K-i for the inhibition of free factor Xa of 323.5 pM, In plasma-based clotting time assays, AcAP was more effective at prolonging the prothrombin time than both r ecombinant hirudin and tick anticoagulant peptide. These data suggest that AcAP, a specific inhibitor of factor Xa, is one of the most poten t naturally occurring anticoagulants described to date.