Anticoagulants and their uses
OwnerNils Von Sicard, Michael Morris +2inventors
InventorsNils Von Sicard, Michael Morris, Asgar Electricwala, Roger Munro
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Abstract
The present invention relates to the identification of a specific inhibitor of the extrinsic clotting pathway from triatomine bugs, which we have designated TEPI (triatomine extrinsic pathway inhibitor). In one embodiment, the polypeptide inhibitor or fragment has a N-terminal sequence: 1 A-Met-Val-Thr-Asn-X-Asn-Met-Pro-Asn-Pro-Met-Thr- Gly-Phe-Glu-Lys-Ser-X-Phe-Phe-Thr-X-Met-Trp-Tyr- Val- wherein X indicates any amino acid sequence residue or pharmaceutically acceptable salt thereof and A represents Ser, Asp or Glu, and preferably Ser.
Claims19
A polypeptide inhibitor of the extrinsic clotting pathway, as obtainable from triatomine bugs, having N-terminal sequence:
- A-Met-Val-Thr-Asn-X-Asn-Met-Pro-Asn-Pro-Met-Thr-Gly-Phe-Glu-Lys-Ser-X-Phe-Phe-Thr-X-Met-Trp-Tyr-Val-
- wherein X indicates any amino acid sequence residue or pharmaceutically acceptable salt thereof and A represents Ser, Asp or Glu, and preferably Ser.
The polypeptide inhibitor of any one of the preceding claims, wherein the polypeptide inhibitor has a molecular mass of about 20 kDa as determined by SDS-PAGE.
The polypeptide inhibitor of any one of the preceding claims, wherein the inhibitor is capable of increasing the prothrombin time (PT) and has substantially no effect on the activated partial thromboplastin time (APTT).
The polypeptide inhibitor of any one of the preceding claims, wherein the inhibitor has substantially no effect on the thrombin clotting time (TCT).
A nucleic acid probe which comprises a sequence which encodes a polypeptide sequence as represented by:
- A-Met-Val-Thr-Asn-X-Asn-Met-Pro-Asn-Pro-Met-Thr-Gly-Phe-Glu-Lys-Ser-X-Phe-Phe-Thr-X-Met-Trp-Tyr-Val-
- wherein X indicates any amino acid sequence residue or pharmaceutically acceptable salt thereof and A represents Ser, Asp or Glu, and preferably Ser.
Dependencies are inferred from the claim text.