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Research Interests

Organic & Bioorganic Chemistry/Chemical Biology

Research program in my group is directed towards the interface of organic chemistry and molecular biology/cell biology, namely chemical biology and chemical genetics. 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. Current research projects center around the following areas:

(1) Combinatorial Chemistry & Organic Synthesis. By utilizing combinatorial approaches, we are synthesizing libraries of small molecules that possess novel fluorescent properties. We are also exploiting the possibility of making encoded small molecule and peptide-based libraries suitable to make the corresponding, addressable microarrays. Other interests include developing one-bead, two-compound strategies for high-throughput screening (HTS) of peptide and non-peptide protease (and other enzymes) inhibitors, as well as developing combinatorial approaches towards novel chiral catalysts.

(2) De Novo Peptide & Protein Design. Both rational design and combinatorial approaches (semi-rational/irrational) are being utilized in our group to design peptides and proteins that possess novel properties in their folding and chemical activities, etc. For example, can functional proteins composed of less than the 20 naturally occurring amino acids (i.e. 15 AA) exist? Techniques that we use include phage display, DNA shuffling, cloning, protein expression, solid-phase peptide synthesis and chemical protein synthesis.

(3) Genomics/Functional Genomics & Biochip technologies. DNA microarray technology has made it possible to look at differential transcription profiles at the whole genome scale. Research in our group focuses on using this powerful technology to look at how natural products affect human diseases (cancer, TB, etc.) at their genetic levels. With the information obtained, ultimately we hope to be able to design better drugs that combat these diseases. In addition, we are interested in developing next-generation biochips (protein chips, peptide chip, small molecule chips, etc.), which we believe will play a major role in biotechnology in the post-genomic era. An automatic microarray spotter has been set up in the lab. Together with our expertise in combinatorial chemistry, organic synthesis and molecular biology, we are currently exploring a number of approaches, each of which will lead to high-throughput deposition of thousands of different functional molecules (proteins, peptides, small molecules, etc.) onto different locations of a microscope glass slides (1" x 2").

Representative Publications

(For complete publication list, click here

1. Hu, Y.; Chen, G.Y.J.; Yao, S.Q. "Activity-based high-throughput screening of enzymes using DNA microarray", Angew. Chem. Intl. Ed. 2005, 44, 1048-1053.
2. 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., 2005, 596-598.
3. Uttamchandani, M.; Walsh, D.P.; Yao, S.Q.*; Chang, Y.T. Small molecule microarrays · recent advances and applications·, Curr. Opin. Chem. Biol., 2005, 9, 4-13.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Wang G., Yao, S. Q. "Combinatorial synthesis of a small molecule library based on vinyl sulfone scaffold", Org. Lett. 2003, 5, 4437-4440.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.