Covalently dimerized bivalent binding agents
作者： John C. Zwaagstra , Traian Sulea , Maria L. Jaramillo , Maureen D. O'connor-Mccourt , Catherine Collins
DOI:
关键词: Receptor 、 Bivalent (genetics) 、 Covalent bond 、 Cysteine 、 Cleave 、 Stereochemistry 、 Chemistry 、 Dimer 、 Binding domain 、 Fusion protein
摘要: The present invention addresses limitations of prior art receptor-based traps through a methodology called the clamp/click/cleave (CCC) approach. Two fusion proteins each comprising binding domain fused to coiled-coil are non-covalently dimerized (clamp), and dimer so formed is stabilized by covalent disulphide bond (click) between cysteine residues located on domains coiled-coils. Once has formed, coiled-coils subsequently removed (cleave) cleaving fusions at cleavage sites provide covalently bivalent agent invention. Such agents useful in treatment diagnosis disease states characterized production and/or overexpression ligand which bind. particularly for where receptor ligand-binding domains, such as those TGF-β receptors.
lens.org参考文章(20)
Gregory De Crescenzo, Heman Chao, John Zwaagstra, Yves Durocher, Maureen D. O’Connor-McCourt, Engineering TGF-β Traps: Artificially Dimerized Receptor Ectodomains as High-affinity Blockers of TGF-β Action Humana Press. pp. 671- 684 ,(2008) , 10.1007/978-1-59745-293-9_40
Yu-an Yang, Lalage Wakefield, Transforming growth factor beta (TGF-beta) antagonist selectively neutralizes "pathological" TGF-beta ,(2002)
John Zwaagstra, Beatrice Paul-Roc, Maria Jaramillo, Gregory De Crescenzo, Myriam Banville, Maureen D. O'Conner, Coiled-coil fusion proteins comprising cell receptor domains ,(2004)
Alexander A Kortt, Olan Dolezal, Barbara E Power, Peter J Hudson, Dimeric and trimeric antibodies: high avidity scFvs for cancer targeting. Biomolecular Engineering. ,vol. 18, pp. 95- 108 ,(2001) , 10.1016/S1389-0344(01)00090-9
J. Holash, S. Davis, N. Papadopoulos, S. D. Croll, L. Ho, M. Russell, P. Boland, R. Leidich, D. Hylton, E. Burova, E. Ioffe, T. Huang, C. Radziejewski, K. Bailey, J. P. Fandl, T. Daly, S. J. Wiegand, G. D. Yancopoulos, J. S. Rudge, VEGF-Trap: A VEGF blocker with potent antitumor effects Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 11393- 11398 ,(2002) , 10.1073/PNAS.172398299
Robert S. Hodges, Boehringer Mannheim award lecture 1995. La conference Boehringer Mannheim 1995. De novo design of alpha-helical proteins: basic research to medical applications. Biochemistry and Cell Biology. ,vol. 74, pp. 133- 154 ,(1996) , 10.1139/O96-015
Cyril Boucher, Benoît Liberelle, Mario Jolicoeur, Yves Durocher, Gregory De Crescenzo, Epidermal growth factor tethered through coiled-coil interactions induces cell surface receptor phosphorylation. Bioconjugate Chemistry. ,vol. 20, pp. 1569- 1577 ,(2009) , 10.1021/BC9001147
Zhizhong Li, Hui Wang, Christine E. Eyler, Anita B. Hjelmeland, Jeremy N. Rich, Turning cancer stem cells inside out: an exploration of glioma stem cell signaling pathways. Journal of Biological Chemistry. ,vol. 284, pp. 16705- 16709 ,(2009) , 10.1074/JBC.R900013200
Sophie Broussau, Nadine Jabbour, Guillaume Lachapelle, Yves Durocher, Rosanne Tom, Julia Transfiguracion, Rénald Gilbert, Bernard Massie, Inducible Packaging Cells for Large-scale Production of Lentiviral Vectors in Serum-free Suspension Culture Molecular Therapy. ,vol. 16, pp. 500- 507 ,(2008) , 10.1038/SJ.MT.6300383
Chichi Huang, Receptor-Fc fusion therapeutics, traps, and MIMETIBODY technology. Current Opinion in Biotechnology. ,vol. 20, pp. 692- 699 ,(2009) , 10.1016/J.COPBIO.2009.10.010