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Your search keyword '"Roberta S. Batorsky"' showing total 2 results
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2 results on '"Roberta S. Batorsky"'

1. Demonstration of a Genetic Therapeutic Index for Tumors Expressing Oncogenic BRAF by the Kinase Inhibitor SB-590885

Author

Roberta S. Batorsky, Jerry L. Adams, Shu Yun Zhang, Michael D. Schaber, Rakesh Kumar, Julie Lougheed, Thomas J. Stout, Erin Hugger, Meenhard Herlyn, David Chau, Maureen L. Ho, Ami S. Lakdawala, Earl May, Rooja G. Contractor, Jae Lee, Pearl S. Huang, Andrew K. Takle, Hieu T. Do, Lusong Luo, David M. Wilson, Michael M. Morrissey, Lifu Wang, Cynthia M. Rominger, David A. Tuveson, Alastair J. King, Denis R. Patrick, David W. Rusnak, Keiran S.M. Smalley, and Florian A. Karreth

Subjects
Models, Molecular, Proto-Oncogene Proteins B-raf, Cancer Research, Protein Conformation, Blotting, Western, Mice, Nude, Biology, Crystallography, X-Ray, medicine.disease_cause, Mice, Cell Movement, Mutant protein, Cell Line, Tumor, Neoplasms, Gene expression, medicine, Animals, Humans, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Protein Kinase Inhibitors, Alleles, Cell Proliferation, Molecular Structure, Kinase, Imidazoles, Xenograft Model Antitumor Assays, Molecular biology, Blot, Oncology, Protein kinase domain, Mechanism of action, Cell culture, Mutation, Cancer research, Female, medicine.symptom, Crystallization, Carcinogenesis, HT29 Cells
Abstract

Oncogenic BRAF alleles are both necessary and sufficient for cellular transformation, suggesting that chemical inhibition of the activated mutant protein kinase may reverse the tumor phenotype. Here, we report the characterization of SB-590885, a novel triarylimidazole that selectively inhibits Raf kinases with more potency towards B-Raf than c-Raf. Crystallographic analysis revealed that SB-590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration, which is distinct from the previously reported mechanism of action of the multi-kinase inhibitor, BAY43-9006. Malignant cells expressing oncogenic B-Raf show selective inhibition of mitogen-activated protein kinase activation, proliferation, transformation, and tumorigenicity when exposed to SB-590885, whereas other cancer cell lines and normal cells display variable sensitivities or resistance to similar treatment. These studies support the validation of oncogenic B-Raf as a target for cancer therapy and provide the first evidence of a correlation between the expression of oncogenic BRAF alleles and a positive response to a selective B-Raf inhibitor. (Cancer Res 2006; 66(23): 11100-5)

Published
2006

2. Biosynthetic antibody binding sites: Development of a single-chain Fv model based on antidinitrophenol IgA myeloma MOPC 315

Author

John E. McCartney, Lynne Lederman, Gay-May Wu, James S. Huston, Roberta S. Batorsky, Hermann Oppermann, Eric A. Drier, and Nancy A. Cabral-Denison

Subjects
Protein Conformation, Recombinant Fusion Proteins, Molecular Sequence Data, Biochemistry, law.invention, Mice, Antigen, law, Animals, Bioorganic chemistry, Amino Acid Sequence, Binding site, Base Sequence, biology, Chemistry, DNA, Protein engineering, Fusion protein, Molecular biology, Recombinant DNA, biology.protein, Specific activity, Binding Sites, Antibody, Antibody, Multiple Myeloma, Dinitrophenols
Abstract

The functional antigen binding region of antidinitrophenol mouse IgA myeloma MOPC 315 has been produced as a single-chain Fv (sFv) protein in E. coli. Recombinant 315 proteins included sFv alone, a bifunctional fusion protein with amino-terminal fragment B (FB) of staphylococcal protein A, and a two-chain 315 Fv fragment. Successful refolding of the 315 sFv required formation of disulfide bonds while the polypeptide was in a denatured state, as previously observed for the parent Fv fragment. Affinity-purified recombinant 315 proteins showed full recovery of specific activity, with values for Ka,app of 1.5 to 2.2 x 10(6) M-1, equivalent to the parent 315 Fv fragment. As observed for natural 315 Fv, the sFv region of active FB-sFv315 fusion protein was resistant to pepsin treatment, whereas inactive protein was readily degraded. These experiments will allow the application of protein engineering to the 315 single-chain Fv; such studies can advance structure-function studies of antibody combining sites and lead to an improved understanding of single-chain Fv proteins.

Published
1991

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