NUS Graduate School for Integrative Sciences and Engineering

YAO Shao Qin

Research Areas
Brief Description of Research
1. Chemical Biology
2. Proteomics
3. Medicinal Chemistry
4. Nanobiotechnology
5. Protein Engineering

A key step towards the biological characterization of enzymes, as well as their adoption as drug targets, is the development of global solutions that bridge the gap in understanding these proteins and their interactions. We herein present technological advances that facilitate the study of enzymes and their properties both in vitro and in living organisms (e.g. live mammalian cells/tissues). This is an emerging area we called “Catalomics”, which involves the development of powerful strategies in Chemical Biology and Chemical Proteomics that enable organism-wide, high-throughput studies of enzymes.

Over the years, our group has introduced and developed a variety of such enabling platforms for many classes of enzymes, including kinases, phosphatases and proteases, as well as proteins that engage in interactions with them leading to modulating their biological activities. For each of these different types of enzymes, specific design considerations are required to develop the appropriate chemical tools to characterize each class. These tools include activity-based probes and chemical compound libraries, which in many cases are rapidly assembled using efficient combinatorial synthesis or “click chemistry” strategies. The resulting molecular assortments may then be screened against the target enzymes in high-throughput using microplates or microarrays. Once “hits” are identified, they will be further studied in live mammalian cells/disease tissues. In cases where compounds are not cell-permeable and/or possess unfavorable cytotoxicity, they will be delivered into cells/tissues in cell/tissue type-specific manner, and their intracellular release is done in a “smart” manner that is highly controllable and directly dependent upon the disease state of the intracellular settings. These techniques offer powerful means to study, profile, and discover potent small molecules that can modulate enzyme activity. Specific foci in “Catalomics” are:

  • Organic synthesis, combinatorial & medicinal chemistry; Solid-phase synthesis of natural product-like and bioactive compounds; Click chemistry; Multicomponent reactions
  • Proteomics/functional Genomics & catalomics; Developing next-generation microarray technologies; Developing new strategies for large-scale proteomics and drug profiling; Microarrays for disease diagnostics
  • Protein engineering & directed evolution; Protein- and peptide-based biosensors; In vitro and in-cell evolution of proteins with diverse functions; protein-protein interaction and post-translational modifications
  • Small molecule bioimaging of cellular events; Developing novel strategies for biomolecule labeling in living cells; Developing novel fluorescent molecules; Developing strategies for transporting macromolecules across cell membranes