Peptides and Their Utility in Modulation of Behavior of Cells Expressing alpha3beta1 Integrins
Description of Invention:
The present invention relates generally to peptides that bind to or are recognized by alpha3beta1 integrins and in particular, to pharmaceutical compositions containing and methods of using said peptides to inhibit or promote various functions of cells that express alpha3beta1 integrins.
Integrins are transmembrane alpha, beta-heterodimer receptors expressed on a wide variety of cells which are involved in extracellular matrix (ECM) interactions. Experimental data has shown that the ECM can affect gene expression and that this altered gene expression can change the composition of the ECM. A bi-directional exchange of information between cells and their surrounding matrix is therefore taking place and because of this communication, integrins can control cell growth, motility, differentiation and survival. Defects in the regulation of these processes can result in many disease states, such as inheritable developmental disorders, defective wound repair, hematological disorders, cardiovascular diseases, immunological disorders, neurodegenerative diseases and cancer initiation, invasion and metastasis. The disclosed peptides have been shown to inhibit angiogenesis, cell adhesion and proliferation and wound repair when administered in a soluble form; however, when the same peptides are immobilized on a substratum, they promote adhesion and proliferation of endothelial cells. Thus by controlling the conditions, these peptides can be used to generate specific responses. Specific applications for the peptides include the treatment of angiogenesis-mediated diseases, production of vascular grafts and artificial blood vessels.
Inventors:
David D. Roberts and Henry C. Krutzsch (NCI)
Patent Status:
DHHS Reference No. E-169-1999/0 --
U.S. Patent No. 7,129,052 issued 31 Oct 2006
U.S. Patent Application No. 11/466,718 filed 23 Aug 2006
Relevant Publication: J Furrer, B Luy, V Basrur, DD Roberts, JJ Barchi Jr. Conformational analysis of an alpha3beta1 integrin-binding peptide from thrombospondin-1: implications for antiangiogenic drug design. J Med Chem. 2006 Oct 19;49(21):6324-6333. [PubMed abs]
Portfolios: Internal Medicine
Internal Medicine-Therapeutics
For Additional Information Please Contact: Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/451-7337
Email: hastingw@mail.nih.gov
Fax: 301/402-0220
