A novel platelet inhibitor from bloodfeeding hookworms

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41HL072749-01
Agency Tracking Number: HL072749
Amount: $99,383.00
Phase: Phase I
Program: STTR
Awards Year: 2003
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
BOX 8175, BOX 8175, New Haven, CT, 94904
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 MICHAEL CAPPELLO
 (203) 737-4320
 MICHAEL.CAPPELLO@YALE.EDU
Business Contact
 MARTIN MATTESSICH
Phone: (203) 737-1952
Email: MJMATT@IX.NETCOM.COM
Research Institution
 YALE UNIVERSITY
 47 COLLEGE STREET, SUITE 203
NEW HAVEN, CT, 06520
 Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Thromboembolic disease is a major cause of morbidity and mortality in the developed world. Because platelets play a critical role in the activation and propagation of thrombosis, they represent important targets for new anti-thrombotic drugs. A potent inhibitor of human platelet function has been isolated from the bloodfeeding hookworm, Ancylostoma caninum. This novel protein is the first naturally occurring compound shown to block the binding of platelet integrins GPIIb/IIIa and GPIa/IIa, the cell surface receptors for fibrinogen and collagen, respectively. The objective of this Phase I STTR grant application is to purify milligram quantities of active recombinant hookworm platelet inhibitor (rHPI) suitable for testing in vivo and in vitro. The rHPI will be characterized using whole platelet assays of aggregation and adhesion. In addition, quantitative experiments will measure the ability of rHPI to block the interaction of collagen and fibrinogen with their respective integrin receptors. Competition experiments with various peptides will delineate HPI binding sites and further characterize its molecular mechanism of action. Lastly, truncated variants of rHPI will be produced in order to determine the smallest protein domain with preserved antiplatelet activity. The long-term objective is to develop rHPI as a therapeutic agent for the treatment of thrombotic disorders in humans.

* Information listed above is at the time of submission. *

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