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.
The retaining β-Kdo glycosyltransferase WbbB uses a double-displacement mechanism with an intermediate adduct rearrangement step.
Forrester TJB, Ovchinnikova OG, Li Z, Kitova EN, Nothof JT, Koizumi A, Klassen JS, Lowary TL, Whitfield C, Kimber MS
Nature Communications (2022)
The biosynthetic origin of ribofuranose in bacterial polysaccharides.
Kelly SD, Williams DM, Nothof JT, Kim T, Lowary TL, Kimber MS, Whitfield C
Nature Chemical Biology (2022)
A De Novo Route to 3,6-Dideoxy Sugars.
Yang S, Chu CJ, Lowary TL
Organic Letters (2022)
Synthesis of a Tridecasaccharide Lipooligosaccharide Antigen from the Opportunistic Pathogen Mycobacterium kansasii.
Shen K, Bai B, Liu YH, Lowary TL
Angewandte Chemie-International Edition (2021)
Synthesis of structurally-defined polymeric glycosylated phosphoprenols as potential lipopolysaccharide biosynthetic probes.
Wang L, Lowary TL
Chemical Science (2021)
Synthesis of a Highly Branched Nonasaccharide Chlorella Virus N-Glycan Using a “Counterclockwise” Assembly Approach.
Lin S, Lowary TL
Organic Letters (2020)
Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study.
Broger T, Sossen B, du Toit E, Kerkhoff AD, Schutz C, Ivanova Reipold E, Ward A, Barr DA, Macé A, Trollip A, Burton R, Ongarello S, Pinter A, Lowary TL, Boehme C, Nicol MP, Meintjes G, Denkinger CM
The Lancet Infectious Diseases (2019)
A Convergent Route to Enantiomers of the Bicyclic Monosaccharide Bradyrhizose Leads to Insight into the Bioactivity of an Immunologically Silent Lipopolysaccharide.
Aboussafy CL, Andersen Gersby LB, Molinaro A, Newman MA, Lowary TL
J. Org. Chem. (2019)
Synthesis of the Campylobacter jejuni 81-176 strain capsular polysaccharide repeating unit reveals the absolute configuration of its O-methyl phosphoramidate motif.
Thota VN, Ferguson MJ, Sweeney RP, Lowary TL
Angew. Chem. Intl. Ed. (2018)
Insights into Interactions of Mycobacteria with the Host Innate Immune System from a Novel Array of Synthetic Mycobacterial Glycans.
Zheng RB, Jégouzo SAF, Joe M, Bai Y, Tran HA, Shen K, Saupe J, Xia L, Ahmed MF, Liu YH, Patil PS, Tripathi A, Hung SC, Taylor ME, Lowary TL, Drickamer K
ACS Chem. Biol. (2017)