Charles Loh

Charles Loh

Research Group Leader, Chemical Biology

Dazzling Synthesis with Creativity, Targeting Bioactivity with Flair

Research Concept

The research work in the Loh research group draws upon nature inspired non-covalent catalysis concepts in developing novel glycosylation reactions. Our multidisciplinary expertise in synthesis and cell-based phenotypic assays opens up a plethora of opportunities to answer fundamental questions at the interface of modern catalysis and carbohydrate chemistry. By expediting development of synthetic methodologies, it is our aim to synthetically enable unprecendented access into carbohydrate based molecular probes. Currently, our research group has successfully demonstrated our concept, that the development of powerful hydrogen bonding and halogen bonding catalyzed strain-release glycosylations opens up a new class of non-smoothened Hedgehog signaling glycosidic inhibitors.

In all, we seek to address longstanding challenges in the glycosciences by the following key approaches:

a) Biomimetic Synthesis. By developing new catalytic glycosylation methodologies, through mimicking how glycosyl transferases exploits noncovalent interactions in nature, we strive to access complex small molecule synthetic glycosides bearing subtle stereochemical differences with precision. The chemistry programme is highly mechanistically driven, and intensive investigation into reaction kinetics allow fundamental understanding how intricacies in glycosylation mechanisms affect effectiveness and selectivity in glycosidic bond construction.

Our vision is to use frontier chemistry to open up access unexplored sp3-rich glycosidic chemical space.

b) Phenotypic Screening. Capitalizing on a forward chemical genetics approach, we exploit phenotypic screening to unravel hitherto unknown biological activity in synthetic glycosides, particularly those related to oncologically relevant signaling pathways.

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