Potent Anti-Coagulant Activity of a Novel Protein from the Sand Fly Lutzomyia longipalpis
Posted Jul 28 2009 5:00pm
Description of Invention: The salivary gland lysates of Lutzomyia longipalpis, the New World sand fly and main vector for visceral leishmaniasis, contain an anti-coagulant protein that helps the fly complete its blood meal. This invention relates to the identification of LJL143, a salivary gland protein of L. longipalpis, as a specific inhibitor of coagulation factor Xa. LJLl43 is secreted in the saliva of L. longipalpis and exerts its effects by tightly binding the catalytic site of factor Xa. By directly binding the catalytic site, it is believed that the potent anti-coagulant activity of LJL143 will be accompanied by reduced side effects compared to anti-coagulant drugs that rely on activating serine proteases. LJL143 has a novel sequence with no reported homology in the gene bank, and is the first anticoagulant factor identified in sand flies.
LJLl43 may be used for inhibiting Factor Xa activity in vivo or as a prototype for designing specific inhibitors of Factor Xa. Because of its high specificity, LJLl43 may be used as an anticoagulant in a number of pro-coagulant diseased states including deep venous thrombosis, coronary artery disease, non-hemorrhagic stroke, and unstable angina with potentially reduced side effects.
Safe and effective anti-coagulant for therapeutic use
Treatment of several conditions such as deep venous thrombosis, coronary artery disease, non-hemorrhagic stroke, and unstable angina
Advantages: May be safer than other important blood thinning drugs such as Warfarin.
JG Valenzuela, M Garfield, ED Rowton, VM Pham. Identification of the most abundant secreted proteins from the salivary glands of the sand fly Lutzomyia longipalpis, vector of Leishmania chagasi. J Exp Biol. 2004 Oct;207(Pt 21):3717-3729. [ PubMed abs ]
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