Modified heparin binding growth factors

Details Modified heparin binding growth factors Modified heparin binding growth factors

C - Chemistry, Metallurgy

12

N

C12N 15/18 (2006.01) A61K 38/18 (2006.01) C07K 14/39 (2006.01) C07K 14/475 (2006.01) C07K 14/50 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2079604

2079604 9115229 PCTABS00007 This invention provides modified heparin binding growth factors (HBGFs). In particular, this invention provides a modified HBGF-1, an angiogenic polypeptide mitogen for mesoderm- and neuroectoderm-derived cells in vitro, that remains biologically active after deletion of the NH2-terminal domain (1-20; .alpha.) of the HBGF-1.beta. precursor. Using polymerase chain reaction mutagenesis and prokaryotic expression systems, a mutant of HBGF-1.alpha. lacking the nuclear translocation sequence, residues 21-27 (NYKKPKL; HBGF-1U) was prepared. HBGF-1U, like HBGF-1.alpha., binds to heparin, induces intracellular receptor-mediated tyrosine phosphorylation and the expression of the c-fos mRNA transcript, HBGF-1U does not stimulate DNA synthesis or cell proliferation. This invention also provides chimeric proteins in which the biological activity of the HBGF family member has been reconstituted. In particular, this invention provides a chimeric protein, HBGF-1U2, which contains HBGF 1U and the well-known histone 2B NTS sequence, GKKRKSKAK, at the amino-terminus. HBGF-1U2 has full mitogenic activity restored. This invention, thus, provides HBGF peptides that lack mitogenic activity and means to restore this activity. In addition, this invention provides peptides, HBGF-1U, that can be used as an antagonist of HBGF-1 function, particularly during events involving angiogenesis in vivo. Finally, this invention provides a method of treating diseases that involve pathological proliferation of endothelial cells, such as cancer, psoriasis, and arthritis.

Affiliated with

Also associated with

Rating

Modified heparin binding growth factors does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Modified heparin binding growth factors, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Modified heparin binding growth factors will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFCA-PAI-O-1729493