Our research program is focused in the areas of synthetic chemistry (with a particular emphasis in carbohydrate chemistry), the conformational analysis of oligosaccharides and the design of novel therapeutic agents that act by inhibiting carbohydrate-processing enzymes. Students and postdoctoral fellows in the group use synthetic chemistry to prepare compounds with interesting biological activities and then have the opportunity to use them in either biochemical or conformational studies.
The primary research focus is directed ultimately towards the identification of new drugs for the treatment of tuberculosis. Our approach is to develop inhibitors of the enzymes that assemble the polysaccharide portions of the protective cell wall of the organism responsible for this disease, Mycobacterium tuberculosis. These polysaccharides are unique in that they are comprised largely of monosaccharides in the furanose ring form. The synthesis of these compounds has been largely neglected by synthetic chemists and our efforts involve both total synthesis and the development of new synthetic methods.
We have completed the total synthesis of a 22-residue oligosaccharide that is an important motif found in the mycobacterial cell wall and fragments of this oligosaccharide, and related analogues, are currently being synthesized and explored in the development of novel vaccines for the prevention of tuberculosis. We are also working towards the characterization of glycosyltransferases involved in mycobacterial cell wall biosynthesis.
A Convergent Route to Enantiomers of the Bicyclic Monosaccharide Bradyrhizose Leads to Insight into the Bioactivity of an Immunologically Silent Lipopolysaccharide.
Aboussafy, C. L.; Andersen Gersby, L. B.; Molinaro, A.; Newman, M.-A.; Lowary, T. L.
J. Org. Chem. (2019)
Characterization of the Antigenic Heterogeneity of Lipoarabinomannan (LAM), the Major SurfaceGlycolipid of Mycobacterium tuberculosis, and Complexity of Antibody Specificities toward This Antigen.
Choudhary, A.; Patel, D.; Honnen, W.; Lai, Z.; Prattipati, R.; Zheng, R. B.; Hsueh, Y-C.; Gennaro, M. L.; Lardizabal, A.; Joe, M.; Bai. Y.; Shen, K.; Spencer, J.; Chatterjee, D.; Broger, T.; Lowary, T. L.; Pinter, A.
J. Immunol. (2018)
Synthesis of the Campylobacter jejuni 81-176 strain capsular polysaccharide repeating unit reveals the absolute configuration of its O-methyl phosphoramidate motif.
Thota, V. N.; Ferguson, M. J.; Sweeney, R. P.; Lowary, T. L.
Angew. Chem. Intl. Ed. (2018)
Synthesis of the highly branched hexasaccharide core of chlorella virus N-linked glycans.
Lin, S.; Lowary, T. L.
Chem Eur J. (2018)
Insights into mycobacteria interactions with the host innate immune system from a novel array of synthetic mycobacterial glycans.
Zheng, R.B.; Jégouzo, S. A. F.; Joe, M.; Bai, Y.; Tran, H. A.; Shen, K.; Saupe, J.; Xia, L.; Ahmed, M. F.; Liu, Y.-H.; Patil, P. S.; Tripathi, A.; Hung, S.-C.; Taylor, M. E.; Lowary, T. L.; Drickamer, K.
ACS Chem. Biol. (2017)
Association of Human Antibodies to Arabinomannan with Enhanced Mycobacterial Opsonophagocytosis and Intracellular Growth Reduction.
Chen, T.; Blanc, C.; Eder, A. Z.; Prados-Rosales, R.; Oliveira-Souza, A. C.; Kim, R. S.; Glatman-Friedman, A.; Joe, M.; Bai, Y.; Lowary, T. L.; Tanner, R.; Brennan, M. J.; Fletcher, H. A.; McShane, H.; Casadevall, A.; Achkar, J. M.
J. Infect. Dis. (2016)
Effect of phenolic glycolipids from Mycobacterium kansasii on proinflammatory cytokine release. A structure–activity relationship study.
Elsaidi, H. R. H.; Lowary, T. L.
Chem. Sci. (2015)
Synthesis of Carbohydrate Methyl Phosphoramidates.
Ashmus, R. A.; Lowary, T. L.
Org. Lett. (2014)
Tetrameric structure of GlfT2 reveals a scaffold for the assembly of mycobacterial arabinogalactan.
Wheatley, R. W.; Zheng, R. B.; Richards, M. R.; Lowary, T. L.; Ng, K. K. S.
J. Biol. Chem. (2012)
Synthesis of the Docosanasaccharide Arabinan Domain of Mycobacterial Arabinogalactan and a Proposed Octadecasaccharide Biosynthetic Precursor.
Joe, M.; Bai, Y.; Nacario, R. C.; Lowary, T. L.
J. Am. Chem. Soc. (2007)