Principal Investigators:
Leslie I. Gold, Ph.D., Department of Pathology, New York University School of Medicine
Iain D. Campbell, Ph.D., Department of Biochemistry, Oxford University

Background
Following wounding, a complex series of cellular and biochemical reactions occur, culminating in clot formation and the sealing of damaged blood vessels. The critical final events in clot formation are the proteolytic conversion of a plentiful circulating soluble plasma protein, fibrinogen, into fibrin and it's subsequent polymerization into a tough, insoluble fibrous matrix. This process is highly controlled and localized only at the site of the tissue insult. Sites of intravascular injury and atherosclerotic lesions are also predisposed to intravascular formation of fibrin clots, a condition known as thrombosis, which may lead to a variety of different clinical manifestations including myocardial infarction.

Description of the Project
Dr. Gold's laboratory has long been interested in the process of wound healing, and the role that fibronectin (Fn) plays in this process. During Dr. Gold's research in this area she discovered and identified physical sites on Fn that bind to fibrin. The physical binding interaction between Fn and fibrin is critical to fibrin clot formation, as an necessary step in the wound repair process. Proteins, such as t-PA, that engage in fibrin binding have similar molecular structures however, the Fn dimer shows an affinity of two logs higher than any other fibrin-binding protein. Specifically, Dr. Gold's research has been concerned with the precise localization and the physicochemical and biochemical characterization of the regions of Fn that contribute to the high fibrin-binding affinity of Fn. Initially, this laboratory localized two distinct but structurally related fibrin-binding sites within Fn, one in the N-terminal and one in the C-terminal. Using recombinant technology to express different polypeptide sequences from the N-terminus, full fibrin-binding activity was confined to a region of 93 amino acids (amino acid residues 151-244; 10.5 kDa). Solid phase binding assays have revealed that the purified recombinant fibrin-binding peptide (FBP) from the N-terminus of Fn displays at least 90% of the total fibrin-binding capacity of intact Fn. This is the smallest polypeptide sequence ever described that possesses fibrin-binding activity and furthermore, it displays the highest binding affinity of any fibrin-binding peptide reported.

Applications
NYU is seeking a partner to help develop these fibrin-binding peptides (FBP's) for use in both diagnostic and therapeutic applications. Potential applications could include: 1) the use of labelled or derivatized FBP's as in vivo imaging agents (i.e. in SPECT, NMR, PET) to identify sites of thrombosis, fibrin deposition or atherosclerotic plaques; 2) the use of FBP's as vectors for targeting and delivery of thrombolytic agents to such sites; and 3) the use of FBP's directly for treating clotting disorders by either preventing tissue plasminogen activator (tPA) mediated thrombolysis or disregulated fibrinogenesis.

Patent Status
A U.S. patent has issued.

For further information please contact:
New York University
Industrial Liaison/Technology Transfer
650 First Avenue, New York, N.Y. 10016
Tel: (212)263-8178 Fax: (212)263-8189