- Bio-organic chemistry
- De novo protein design
- Bioactive non-natrual oligomers
- NIH-NRSA Postdoctoral Fellow, University of Pennsylvania/DuPont (1998-2001)
- Ph.D., California Institute of Technology (1998)
- B. S., National Taiwan University (1992)
Non-natural amino acid synthesis, solid-phase peptide synthesis, solid-phase chemistry, molecular modeling, biophysical and biochemical characterization
De novo design, or designing proteins from scratch, has been valuable for understanding protein structure and more recently function. Extending the de novo design concept further, my research program focuses on sequence-specific polymers with potential applications in biomedical (biomimetics, pharmaceuticals, bio-materials) and material sciences (supramolecular structures, nanotechnology). Three research areas are being pursued for exploring divergence from natural polypeptides in sidechain functionality, backbone, and topology:
Stabilizing Protein Folds with Fluorinated Amino Acids (divergence in sidechain)
Recently, fluorine containing amino acids have been used to stabilize coiled-coils. To understand the nature of this stabilization (i.e. hydrophobic, desolvation, polar interactions... etc.), we are studying self-assembling peptides, with various custom synthesized fluorine containing amino acids, using biophysical methods. This would facilitate future utilization of fluorinated amino acids for stabilizing other protein folds under extreme conditions (heat, organic solvents, pressure, detergents...) for applications in nanofabrication, industrial processes, bio-material and pharmaceutical sciences.
Development of Bioactive Betapeptides (divergence in backbone)
Betapeptides presents an attractive platform for developing future pharmaceutical agents, since they are known to be non-mutagenic with longer serum lifetime compared to alpha-peptides (proteins). Furthermore, betapeptides are known to adopt various regular-repeating secondary structures. By decorating such structured non-natural backbones with appropriate sidechain functionalities, we are currently pursuing several cancer and HIV targets.
Novel Topologies for Functional Biomimetics (divergence in topology)
One of holy grails in molecular design is to devise functional molecular machines at will. Toward this ambitious goal, we have chosen to first mimic proteins, since proteins are capable of performing a myriad of functions. Furthermore, the molecular recognition and catalytic activity of many proteins depend on their loops. Therefore, we are devising novel topologies as structural and functional mimetics of protein loops, and thus proteins. The basic design involves the loops of interest covalently linked to a cyclic peptide template. Several modular synthetic schemes have been developed involving solid-phase chemistry for generating the biomimetics. Further development would enable the incorporation of non-natural backbones into these topologies for the design of molecular machines.
Selected Recent Publications