National University of Singapore
Publishes on Protein Tyrosine Phosphatases, Plant Stress Responses and Tolerance, Glycosylation and Glycoproteins Research. 15 papers and 462 citations.
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A approximately 3500-member library of bidentate inhibitors against protein tyrosine phosphatases (PTPs) was rapidly assembled using click chemistry. Subsequent high-throughput screening had led to the discovery of highly potent (K(i) as low as 150 nM) and selective MptpB inhibitors, some of which represent the most potent MptpB inhibitors developed to date.
A key challenge in current drug discovery is the development of high-throughput (HT) amenable chemical reactions that allow rapid synthesis of diverse chemical libraries of enzyme inhibitors. The Cu(I)-catalyzed, 1,3-dipolar cycloaddition between an azide and an alkyne, better known as "click chemistry", is one such method that has received the most attention in recent years. Despite its popularity, there is still a lack of robust and efficient chemical strategies that give access to diverse libraries of azide-containing building blocks (key components in click chemistry). We report herein a highly robust and efficient strategy for high-throughput synthesis of a 325-member azide library. The method is highlighted by its simplicity and product purity. The utility of the library is demonstrated with the subsequent "click" synthesis of the corresponding bidentate inhibitors against PTP1B.
Synthesis of a novel unnatural amino acid (2-FMPT) for the solid-phase synthesis of peptide-based probes suitable for target-specific activity-based profiling of protein tyrosine phosphatases from crude proteomes is reported.
We report herein a novel phosphopeptide microarray capable of noncovalently "trapping" catalytically inactive mutants of protein tyrosine phosphatases (PTPs), and its application in high-throughput determination of PTP substrate specificity.
Lactuca sativa L. cv. Panama is a temperate plant, but can be grown in the tropics by only subjecting its roots to 20°C while its aerial portions are exposed to the hot, fluctuating temperatures in the greenhouse. This study showed that in Lactuca sativa L. cv. Panama grown at 20°C root-zone temperature (RZT) in the tropics, the roots were longer with a greater number of root tips and total root surface area, and smaller average root diameter as compared with those of ambient RZT (A-RZT) plants. In plants transferred from 20°C to A-RZT (20°C ⇒ A-RZT) when they were 3 weeks old, rate of increase in root length was decreased as was root tip number and surface area; root thickening was increased. The reverse was observed for plants transferred from A-RZT to 20°C-RZT (A ⇒ 20°C-RZT). Mineral nutrients such as NO3 −, nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), and zinc (Zn) present in the plant shoot and root tissues were also determined. Generally, it was found that 20°C-RZT plants had higher leaf N and P concentrations on the basis of per unit dry weight compared with plants grown at A-RZT. Results also showed that total shoot and root NO3 −, K, Ca, Cu, Fe, Mg, Mn, and Zn accumulation of 20°C-RZT plants were more than A-RZT plants. 20°C ⇒ A-RZT plants suffered from a reduction of total mineral accumulation, and Ar ⇒ 20°C-RZT plants increased in total mineral accumulation. Relationships between RZT, root growth, and mineral composition of the experimental plants are discussed.