Development of new antibiotics and compounds to treat genetic rare diseases
The primary research objective in our lab is in the area of carbohydrate synthesis, chemical and enzymatic, to solve key biological problems by understanding bio-catalysis at the molecular level. These basic tools are tightly associated with two major goals of our research program: development of new antibacterial drugs with commercial value, and the development of carbohydrate-based drugs to treat genetic diseases. The most recent achievements of the group include (1) development of new synthetic compounds that successfully combat pathogenic bacteria and in parallel are able to delay new resistance development; (2) development of new aminoglycoside variants with an ability to fix damaged genes during the translation process; a general tool for the treatment of genetic diseases caused by nonsense mutations.
• J. Kandasamy, D. Atia-Glikin, E. Shulman, K. Shapira, M. Shavit, V. Belakhov T. Baasov. Increased Selectivity toward Cytoplasmic versus Mitochondrial Ribosome Confers Improved Efficiency of Synthetic Aminoglycosides in Fixing Damaged Genes: A Strategy for Treatment of Genetic Diseases Caused by Nonsense Mutations. J. Med. Chem. 55(23), 10630-10643 (2012).
• T. Goldmann, N. Overlack, F. Möller, V. Belakhov, M. van Wyk, T. Baasov, U. Wolfrum, and K. Nagel-Wolfrum. A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation. EMBO Molecular Medicine, 4, 1-14 (2012).
• M. Schalev, J. Kondo, D. Kopelyanskiy, C.L. Jaffe, N. Adir, T. Baasov. Identification of the molecular attributes required for Aminoglycoside activity against Leishmania. PNAS 110 (33), 13333-13338 (2013).
• E. Shulman, V. Belakhov, G. Wei, A. Kendall, E. G. Meyron-Holtz, D. Ben-Shachar, J. Schacht, T. Baasov. Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosomes show decreased ototoxicity: a strategy for the treatment of genetic diseases. J. Biol. Chem. 289(4), 2318-2330 (2014).
• G. Gunn, Y. Dai, M. Du, V. Belakhov, J. Kandasamy, T.R. Schoeb, T. Baasov, D.M. Bedwell, K.M. Keeling. Long-term nonsense suppression therapy with NB84 moderates MPS IH disease progression. Mol. Gen. Metab. 111, 374-381 (2014).