Department of Biological Sciences

Research program in my group is directed towards chemical biology and chemical proteomics. By utilizing our expertise in both organic chemistry and molecular biology. We are interested in designing, identifying, synthesizing and studying biologically interesting molecules, which include small molecules and natural products, peptides and their analogs, as well as natural and unnatural proteins. We are particularly interested in molecules that are relevant to diseases such as cancer, TB, alzheimer's and other related neurological diseases. In addition, we are developing a number of high-throughput techniques critical for functional genomics.

With completion of the Human Genome Project, new tools are needed for speedy discovery of functions new genes and proteins possess. Using state-of-art Instruments, we are working closely with our NUS colleagues in an attempt to develop next-generation tools used for large-scale func-tional genomics and proteomics. Specifically, we are utilizing techniques in Combinatorial Biology & Combinatorial Chemistry and developing novel strategies capable of synthesizing thousands of discrete biomolecules. These biomolecules include, but not limited to, small molecules, peptides and proteins. Advanced robotic system is being used to deposit them in nanolitre-size droplets onto 2" x 1" glass slides.

We are also exploiting the possibility of making self-encoded libraries (10 3 -10 6 in size) of small molecules, peptides and proteins that could potentially be used to obtain the corresponding addressable microarrays via the force of self-assembly.

Another area of our research is de novo design and synthesis of peptides and proteins. Solid-phase peptide synthesis, native chemical ligation, DNA cloning and protein expression are some tools we use in the laboratory to synthesize proteins (and peptides) that contain unnatural residues. By incorporating new functionalities in a protein, we are trying to address some fundamental questions in protein folding, protein-ligand recognition, protein-protein interaction, as well enzyme mechanism and catalysis etc. We are interested in developing novel biochemical sensors using in vitro evolution strategies such as phage display, ribosomal display, and DNA shuffling etc.

Hu, Y.; Chen, G.Y.J.; Yao, S.Q. 'Activity-based high-throughput screening of enzymes using DNA microarray', Angew. Chem. Intl. Ed. 2004, accepted..
Tan, E.L.P.; Panicker, R.C.; Chen, G.Y.J.; Yao, S.Q. 'A proteomic strategy for the identification of caspase-associating proteins', Chem. Commun., 2004, accepted.
Chen, G.Y.J.; Yao, S.Q. 'Lighting the cancer cells with the 'dots', Lancet, 2004, accepted. (invited commentary)
Uttamchandani, M.; Walsh, D.P.; Khersonsky, S.M.; Huang, X.; Yao, S.Q.; Chang, Y.T. 'Microarrays of tagged combinatorial triazine libraries in the discovery of small molecule ligands of Human IgG', J. Comb. Chem. 2004, 6, 862-868.
Chan, E.W.S.; Chattopadhaya, S.; Panicker, R.C.; Huang, X.; Yao, S.Q. 'Developing photo-active affinity probes for proteomic profiling - hydroxamate-based probes for metalloproteases', J. Am. Chem. Soc. 2004, 126, 14435-14446.
Zhu, Q.; Girish, A.; Chattopadhaya, S.; Yao, S.Q. 'Developing novel activity-based fluorescent probes that target different classes of proteases', Chem. Commun. 2004, 1512-1513.
Yeo, S.Y.D., Srinivasan, R.; Chen, G.Y.J.; Yao, S.Q. 'Expanded utilities of the native chemical ligation reaction', Chem. Eur. J. 2004, 10, 4664-4672.
Lue, R.Y.P., Chen, G.Y.J., Hu, Y., Zhu, Q., Yao, S.Q. 'Versatile protein biotinylation strategies for potential high-throughput proteomics', J. Am. Chem. Soc. 2004, 126, 1055-1062.
Zhu, Q.; Huang, X.; Chen, G.Y.J.; Yao, S.Q. 'Design and synthesis of fluorogenic substrates that target protein phosphatases', Tetrahedron Lett. 2004, 45, 707-710.
Yeo, S.Y.D., Srinivasan, R., Uttamchandani, M., Chen, G.Y.J., Zhu, Q., Yao, S.Q. 'Cell-permeable small molecule probes for site-specific labeling of proteins' Chem. Commun., 2003, 2870-2871.
Wang G., Yao, S. Q. 'Combinatorial synthesis of a small molecule library based on vinyl sulfone scaffold', Org. Lett. 2003, 5, 4437-4440.
Zhu, Q., Uttamchandani, M., Li, D.B., Lesaicherre, M.L., Yao, S. Q. 'An enzymatic profiling system in a small-molecule microarray', Org. Lett. 2003, 5, 1257-1260.
Chen, G.Y.J., Uttamchandani, M., Zhu, Q., Wang, G., Yao, S.Q. 'Developing a strategy for activity-based detection of enzymes in a protein microarray', ChemBioChem. 2003, 4, 336-339.
Hu, Y., Wang, G., Chen, G.Y.J., Fu, X., Yao, S.Q. 'Proteome analysis of Saccharomyces Cerevisiae under metal stress by two-dimensional differential gel electrophoresis (DIGE)', Electrophoresis 2003, 24, 1458-1470.
Wang, G., Uttamchandani, M., Chen, G.Y.J., Yao, S.Q. 'Solid-phase synthesis of peptide vinyl sulfones and their uses in large-scale proteomic experiments', Org. Lett. 2003, 5, 737-740.
Lesaicherre, M.L., Lue, Y.P.R., Chen, G.Y.J., Zhu, Q., Yao, S.Q. 'Intein-mediated biotinylation of proteins and its application in a protein microarray', J. Am. Chem. Soc. 2002, 124, 8768-8769.
Spence, M.M., Rubin, S. M., Dimitrov, I.E., Ruiz, E. J., Wemmer, D. E, Pines, A., Yao, S.Q., Tian, F., Schultz, P.G., Functionalized xenon as a biosensor., Proc. Natl. Acad. Sci. USA 2001, 98, 10654-10657.