- 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).
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).
3. 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).
5. Schalev, H. Rozenberg, B. Smolkin, A. Nasereddin, D. Kopelyanskiy, V. Belakhov, T. Schrepfer, J. Schacht, C. L. Jaffe, N. Adir, T. Baasov. Structural Basis for Selective Targeting of Leishmanial Ribosomes: Aminoglycoside Derivatives as Promising Therapeutics. Nucleic Acids Research, 43(17), 8601-8613 (2015).
7. M. Sabbavarapu, M. Shavit, Y. Degani, B. Smolkin, V. Belakhov, T. Baasov. Design of Novel Aminoglycoside Derivatives with Enhanced Suppression of Diseases-Causing Nonsense Mutations. ACS Med. Chem. Lett. 7, 418-423 (2016).
8. Meng, D. Srisai, X. Zhou, W. Cheng, S. Dong, V. Belakhov, Y. Xu, R.D. Palmiter, T. Baasov, Qi Wu. A new inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism. PNAS 113 (13), 3645-3650 (2016).
9. M. Sabbavarapu, T. Pieńko, B-H. Zalman, J. Trylska, T. Baasov. Exploring Eukaryotic Versus Prokaryotic Ribosomal RNA Recognition with Aminoglycoside Derivatives. Med. Chem. Commun. 9, 503-508 (2018).
10. Smolkin, A. Vilevsky, T. Pieńko, M. Shavit, V. Belakhov, J. Trylska, T. Baasov. Towards Catalytic Antibiotics: Redesign of Aminoglycosides to Catalytically Dysable Bacterial Ribosome. ChemBioChem 20, 247-259 (2019).
In general, our lab is interested in the use of organic chemistry, especially carbohydrate chemistry, to solve important biological problems. Our studies involve various chemical and biochemical tools to rationally design and develop novel carbohydrate-based and other structures as new antibiotics that will be able to delay resistance development by bacteria. New concepts we develop include “hybrid antibiotics” and “catalytic antibiotics” as potential strategies to overcome resistance problems. Second project that our lab is engaged considers the development of new small molecule-based drug to treat genetic diseases caused by stop-codon mutations. The compounds we developed are currently in clinical (Phase 2) trials for the treatment of cystic fibroses and cystinosis diseases. Our lab is currently searching for further improvements of these drugs.
Prof. Baasov was born in 1954 in the Soviet Union and immigrated to Israel in 1974, obtained his BSc and MSc from Tel Aviv University and PhD with Mordechai Sheves at the Weizmann Institute (1981-1986). Following a postdoctoral research with J. R. Knowles at Harvard University (Chaim Weizmann Postdoctoral Fellow1986-1988) he joined the Schulich Faculty of Chemistry at the Technion and became Full Professor in 2004. His list of prizes and awards includes the Hershel Rich Innovation Award (2005, 2008, 2010), the Technion Excellence in Teaching Award (seven times: 2002, 2006, 2007, 2008, 2010, 2014, 2015), the Jacknow Award for excellence in teaching (2006), the 2016 ICS-ICL Prize for Technological Innovation, and the 2020 NCK Prize for an Outstanding Medicinal Chemist in Israel. He holds the Irving and Jeanette Benveniste Chair in Life Sciences.
One of the most significant research goals of my lab during the last two decades was the development of safe, nontoxic aminoglycoside (AGs) drugs. We have designed generations of new AGs that are more effective and less toxic than commercially known antibiotics. In addition, we have further developed AG compounds that can overcome genetically inherited diseases, which are induced by the presence of stop-codon mutations. This type of mutations account for about 5-10% of each of 1,800 genetic diseases known to date. Our developed new AGs can allow the ribosome to “read through” the mutation and translate the entire protein, thus alleviating diseases, such as cystic fibroses, Usher’s syndrome, Hurler syndrome, cancer and more. Our remarkable achievement, which was supported by the BSF, NIH and other grants, has eventually led to the establishment of Eloxx Pharmaceuticals in the United States and Israel. One of the developed compounds, ELX-02, is currently in clinical phase 2 trials against stop codon mutations in cystic fibrosis and cystinosis diseases. Other AGs developed in our lab were found to be effective for the treatment of Leishmania, a persistent parasite found in many places around the world, including Israel. Amongst our inventions are bi-functional AGs, which are designed to combat resistant strains of bacteria, as well the innovative concept of catalytic antibiotics.
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