Associate Professor LAM Yulin

B.Sc.(Hons), 1987, National University of Singapore; Ph.D., 1992, National University of Singapore; Research Fellow, 1992-1994 The Scripps Research Institute; Research Fellow, 1994-1996 Institute of Molecular and Cell Biology

Contact Information

Department of Chemistry, NUS 
3 Science Drive 3 
Singapore 117543 

Office: S5-03-04
Tel: (65)-6516-2688
Fax: (65)-6779-1691
Email: chmlamyl@nus.edu.sg


Research Interests

 

Our research interests include (i) bioorganic and medicinal chemistry, and (ii) green chemical synthesis.


BIOORGANIC AND MEDICINAL CHEMISTRY

Cytosolic phospholipase A2 (cPLA2) is an ubiquitous enzyme which is highly selective for glycerophospholipids containing arachidonic acid (AA). There has been much interest to understand the molecular mechanism regulating this enzyme and to develop therapeutics for the treatment of cPLA2-upregulated diseases. Herein we have developed AA derivatives equipped with either one or two fluorescent groups which function as inhibitor      and substrate probes of cPLA2. The inhibition was demonstrated to perform dual functions of inhibition and imaging while the substrate probe could be used for activity assay. [Chem. Commun. 2017, 53, 1813 (DOI 10.1039/C6CC09305A)

Figure shows the targeting of cPLA2 by the newly-designed inhibitor and substrate probes. Left: Identifying differences in cPLA2 level in untreated and Trichostatin A (TSA)-treated SHSY5Y cells. Right: FRET-based assay with the use of substrate probe that demonstrate higher selectivity for cPLA2 against sPLA2

 

We are interested in the synthesis and biological evaluations of novel organic compounds and natural product derivatives as potential anti-cancer, anti-inflammatory and neurological agents

We have devised a versatile synthetic strategy to obtain all the 16 theoretically possible sulfation patterns in the chondroitin sulfate (CS) repeating unit; these include rare but potentially important sulfated motifs which have not been isolated earlier. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231 [Sci. Rep. 2015, 5,14355 (DOI 10.1038/srep14355)].

 

Sphingolipid-metabolizing enzymes control the critical balance of the cellular levels of sphingolipids, including the apoptotic inducing ceramide (Cer) and the proliferative inducing sphingosine 1-phosphate (S1P). The production of S1P, catalyzed by the action of sphingosine kinases (SPHKs), is known to be critical for many cellular processes. However, it is suggested that SPHK, and/or its catalytic product S1P, plays critical roles in various diseases including autoimmune diseases, cancer, and allergies. We have developed 5C, a specific inhibitor of human SPHK1 and demonstrated that inhibition of SPHK1 impairs colony formation and breast tumor formation by MDA-MB-231 cells. In addition, we have also shown that treatment with 5C sensitizes triple negative breast cancers to chemotherapeutic drugs [Oncotarget 2014, Advance Online Publication ISSN: 1949-2553]

 

GREEN CHEMICAL SYNTHESIS

We are also interested in designing new synthetic methodologies that are more environmentally benign, which simplify synthesis and maximize the desired product. We are interested in developing recyclable reagents and catalysts that facilitate reactions in aqueous medium.


Fluorous, oxime-based palladacycle 1 is a thermally stable and versatile precatalyst that efficiently promotes various carbon-carbon bond formation, annulation and carbonylation reactions in aqueous medium under microwave irradiation. Palladacycle 1 gave low levels of Pd leaching and could be reused five times with no significant loss of activity [Green Chem. 201214, 77-80; RSC Advances 2014, 4, 4921-4929; Tetrahedron 2014, 70, 8545-8558; Org. Biomol. Chem. 2015, 13, 1048-1052].


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Representative Publications