Thrombospondin-binding region of histidine-rich glycoprotein and method of use
OwnerRonit Simantov, Roy L. Silversteininventors
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OwnerRonit Simantov, Roy L. Silversteininventors
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Thrombospondin-binding molecules and fragments comprising one or more regions of the TSP-1-binding domains of Histidine-Rich Glycoprotein (HRGP) are provided. Also provided are homologs of TSP-1-binding domains of Histidine-Rich Glycoprotein. Therapeutic methods of use of these thrombospondin-binding molecules and fragments, as well as anti-HRGP antibodies and antibody fragments are disclosed. These methods are useful in modulating a variety of physiological and pathological processes including angiogenesis, inflammatory responses, embryogenesis and tumor proliferation. A range of assay methods for diagnosis and for detection, quantitation and identification of modulators of the TSP-l-binding activity of HRGP are also provided. In addition screening assays for compounds that specifically modulate HRGP expression are provided. These assays are useful in a range of formats from individual assays to library screening as well as high throughput assays. Compounds identified by such methods are useful as therapeutic candidate molecules or as lead compounds in the development of therapeutic molecules.
A protein of molecular weight between about 7 Kd and about 60 Kd, or between about 70 Kd and about 200 Kd, wherein the protein comprises a thrombospondin-binding motif of HRGP.
A pharmaceutical composition comprising a protein which comprises a thrombospondin-binding motif of HRGP, in a pharmaceutically acceptable carrier.
A method of modulating the activity of thrombospondin in a tissue comprising:
A method of identifying a compound that modulates the thrombospondin-binding activity in sample, said method comprising:
A method of activating tissue plasminogen activator comprising:
A method of promoting angiogenesis in the tissues of a mammal comprising administering to the mammal an effective amount of either a) a protein comprising the thrombospondin-binding motif of HRGP, or b) a compound that specifically increases the expression of a protein comprising the thrombospondin-binding motif of HRGP.
A method of inhibiting tumor proliferation in a mammal comprising administering to the mammal an effective amount of either a) an inhibitor of the binding of the thrombospondin-binding motif of HRGP to TSP-1, or b) a compound that inhibits expression of a protein comprising the thrombospondin-binding motif of HRGP.
Dependencies are inferred from the claim text.