Positive modulator of bone morphogenic protein-2

Zamora, Paul O; Pena, Louis A; Lin, Xinhua; Takahashi, Kazuyuki

Positive modulator of bone morphogenic protein-2

Patent · 27 January 2009

OSTI ID:985852

Zamora, Paul O ^[1]; Pena, Louis A ^[2]; Lin, Xinhua ^[3]; Takahashi, Kazuyuki ^[4]

Gaithersburg, MD
Poquott, NY
Plainview, NY
Germantown, MD

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC02-98CH10886

Assignee:: BioSurface Engineering Technologies, Inc. (College Park, MD) Brookhaven Science Associates (Upton, NY)

Patent Number(s):: 7,482,427

Application Number:: 11/064,039

OSTI ID:: 985852

Country of Publication:: United States

Language:: English

References (11)

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Identification of a peptide blocking vascular endothelial growth factor (VEGF)-mediated angiogenesis Binétruy‐Tournaire, Roselyne; Demangel, Caroline; Malavaud, Bernard The EMBO Journal, Vol. 19, Issue 7, p. 1525-1533 https://doi.org/10.1093/emboj/19.7.1525	journal	April 2000
Synthesis of Native Proteins by Chemical Ligation Dawson, Philip E.; Kent, Stephen B. H. Annual Review of Biochemistry, Vol. 69, Issue 1 https://doi.org/10.1146/annurev.biochem.69.1.923	journal	June 2000
A Functional Fibroblast Growth Factor-1 Immunoglobulin Fusion Protein Dikov, Michael M.; Reich, Martha B.; Dworkin, Lydia Journal of Biological Chemistry, Vol. 273, Issue 25, p. 15811-15817 https://doi.org/10.1074/jbc.273.25.15811	journal	June 1998
Influence of BMPs on the Formation of Osteoblastic Lesions in Metastatic Prostate Cancer Feeley, Brian T.; Gamradt, Seth C.; Hsu, Wellington K. Journal of Bone and Mineral Research, Vol. 20, Issue 12 https://doi.org/10.1359/JBMR.050802	journal	August 2005
Identification of a cyclic peptide inhibitor of platelet-derived growth factor-BB receptor-binding and mitogen-induced DNA synthesis in human fibroblasts Brennand, David M.; Dennehy, Ulla; Ellis, Vincent FEBS Letters, Vol. 413, Issue 1, p. 70-74 https://doi.org/10.1016/S0014-5793(97)00885-5	journal	August 1997
Poly(L-lysine) has different membrane transport and drug-carrier properties when complexed with heparin. Shen, W. C.; Ryser, H. J. Proceedings of the National Academy of Sciences, Vol. 78, Issue 12 https://doi.org/10.1073/pnas.78.12.7589	journal	December 1981
BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II Kirsch, Thomas; Nickel, Joachim; Sebald, Walter The EMBO Journal, Vol. 19, Issue 13, p. 3314-3324 https://doi.org/10.1093/emboj/19.13.3314	journal	July 2000
Involvement of bone morphogenic protein‐2 (BMP‐2) in the pathological ossification process of the spinal ligament Tanaka, H.; Nagai, E.; Murata, H. Rheumatology, Vol. 40, Issue 10 https://doi.org/10.1093/rheumatology/40.10.1163	journal	October 2001
Engineering of an FGF–proteoglycan fusion protein with heparin-independent, mitogenic activity Yoneda, Atsuko; Asada, Masahiro; Oda, Yuko Nature Biotechnology, Vol. 18, Issue 6, p. 641-644 https://doi.org/10.1038/76487	journal	June 2000
A heparin binding synthetic peptide from human HIP / RPL29 fails to specifically differentiate between anticoagulantly active and inactive species of heparin Hoke, David E.; Carson, Daniel D.; Höök, Magnus Journal of Negative Results in BioMedicine, Vol. 2, Issue 1 https://doi.org/10.1186/1477-5751-2-1	journal	February 2003

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