Research Lab

Chemical Biology

Chemical inducers of proximity (e.g. molecular glues and bifunctional molecules) are powerful chemical biology tools for the precise and temporal control of various cellular processes. We create these molecules for investigating the posttranslational modifications (PTMs) of disease-related proteins, e.g. Tau & alpha-synuclein.

Drug Discovery

Carbohydrates are essential molecules in health and diseases but rarely explored as drug candidates – presumably due to their high polarity and inherently poor pharmacokinetic properties. We develop drug-like, carbohydrate-based molecule by chemically modify the natural carbohydrate scaffolds.

Medicinal Chemistry

Modern drug discovery has been impeded by the lack of structurally or stereochemically complex small molecules in chemical screening libraries. By late-stage chemical modifications of natural products or existing drug molecules, we create complex drug-like molecules with diverse chemical structures and novel mechanisms of action. Using this strategy, we synthesize pseudo-natural products with potent neuroprotective effects that are not observed in the parental natural products.

1. “Lactone-to-lactam editing alters the pharmacology of bilobalide” Jiang, X., He, X., Wong, J., Scheeff, S., Hau, S.C.K., Wong, T. H., Qin, Y., Fan, C. H., Ma, B., Chung, N. L., Huang, J., Zhao, J., Yan, Y., Xiao, M., Song, X., Hui, T., Zuo, Z., Wu, W.K.K., Ko, H., Chow, K. H.-M. & Ng, B.W.-L.# JACS Au 4, 3537–3546 (2024).
2. “Targeted protein O-GlcNAcylation using bifunctional small molecules” Ma, B., Khan, K.S., Xu, T., Amada, J.X., Guo, Z., Huang, Y., Yan, Y., Lam, H., Cheng, A.S.-L. & Ng, B.W.-L.# J Am Chem Soc 146, 9779–9789 (2024).
3. “Design and synthesis of bicyclo[4.3.0]nonene nucleoside analogues” Scheeff, S., Wang, Y., Lyu, M.-Y., Ahmadabadi, B.N., Hau, S.C.K., Hui, T.K.C., Zhang, Y., Zuo, Z., Chan, R.W.Y.# & Ng, B.W.-L.# Org Lett 25, 9002–9007 (2023).
4. “Palladium-catalyzed arylation of carbasugars enables the discovery of potent and selective SGLT2 inhibitors” Ng, W.-L., Lau, K. M., Lau, C. B. & Shing, T. K. M. Angew Chem Int Ed 55, 13818–13821 (2016).
5. “Coronavirus RNA proofreading: molecular basis and therapeutic targeting” Robson, F., Khan, K.S., Le, T.K., Paris, C., Demirbag, S., Barfuss, P., Rocchi, P., Ng, W.-L.# Molecular Cell 79, 710–727 (2020).