Peptide Inhibitors of Fibronectin and Related Collagen-Binding Proteins
Description of Invention:
Fibronectin has been implicated in a variety of cell contact processes, including cell attachment and migration. Fibronectin interacts with collagen through its gelatin-binding domain and this interaction is fundamental to the organization of extracellular matrices and the behavior of these cells on substrates. Fibronectin is essential for the attachment and migration of many cells, including various tumor and cancer cells.
The issued patents disclose peptide compositions having binding affinity for fibronectin, as well as methods for binding fibronectin with a fibronectin-binding peptide and methods for inhibiting fibronectin-mediated cell adhesion. The peptides disclosed are derived from the extracellular matrix protein thrombospondin, which is a modular adhesive glycoprotein that binds to the gelatin binding domain of fibronectin. These peptides are strong inhibitors of fibronectin-mediated cell adhesion. As such, they may be applicable to a variety of indications including cancer, wound healing, and connective tissue diseases.
Applications:
Potential therapeutic use for applications such as cancer, wound healing, and connective tissue disease.
Research tools for study of cell adhesion and migration processes.
Patent Status:
DHHS Reference No. E-219-1992/0 --
U.S. Patent No. 5,491,130 issued 13 Feb 1996
U.S. Patent No. 5,849,701 issued 15 Dec 1998
Foreign counterparts issued in Australia, Great Britain, France, Germany, and Japan
Related Technologies:
Heparin- and Sulfatide-Binding Peptides From the Type I Repeats of Human Thrombospondin
U.S. Patent No. 5,357,041 issued 18 Oct 1994 (HHS Reference No. E-198-1991/0-US-01)
U.S. Patent No. 5,770,563 issued 23 Jun 1998 (HHS Reference No. E-198-1991/2-US-01)
U.S. Patent No. 6,384,189 issued 07 May 2003 (HHS Reference No. E-019-1994/1-US-02)
Relevant Publication:
JM Sipes, N Guo, E Nègre, T Vogel, HC Krutzsch, DD Roberts. Inhibition of fibronectin binding and fibronectin-mediated cell adhesion to collagen by a peptide from the second type I repeat of thrombospondin. J Cell Biol. 1993 Apr;121(2):469-477. [PubMed abs]
S Schultz-Cherry, H Chen, DF Mosher, TM Misenheimer, HC Krutzsch, DD Roberts, JE Murphy-Ullrich. Regulation of TGFbeta activity by peptides from the type I repeats of thrombospondin-1. J Biol Chem. 1995 Mar 31;270(13):7304-7310. [PubMed abs]
C Daniel, J Wiede, Y Takabatake, M Mizui, Y Isaka, E Imai, H Rupprecht, E Schulze-Lohoff, HC Krutzsch, SMF Ribeiro, DD Roberts, JE Murphy-Ullrich, C Hugo. Thrombospondin-1 is a major activator of TGFbeta in fibrotic renal disease in the rat in vivo. Kidney Int. 2004 Feb;65(2):459-468. [PubMed abs]
Licensing Status:
This technology is no longer available for licensing.
Collaborative Research Opportunity:
The National Cancer Institute, Laboratory of Pathology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these peptides. Please contact John D. Hewes, Ph.D. at (301) 435-3121 or hewesj@mail.nih.gov for more information.
For Additional Information Please Contact: Charlene A. Sydnor Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/435-4689
Email: sydnorc@mail.nih.gov
Fax: 301/402-0220
