Experience

Associate professor (2019 - present) at National Tsing Hua Univ.

Assistant professor (2013 - 2019) at National Tsing Hua Univ.

Research associate (2008 - 2013) at The Scripps Research Institute, La Jolla

Education

Ph.D in Chemistry 2008 with Professor Chi-Huey Wong. The Scripps Research Institute, La Jolla, California

B.S. in Chemistry 1999. National Tsing Hua University, Hsinchu, Taiwan

Small molecules has been wide used to manipulate biological activities through protein receptors, and this strategy has become the norm in the development of inhibitor and probes. While protein arrangement at higher order also control or regulate biological processes such as recognition and signaling, it is difficult to manipulate such processes by molecules provided by general synthetic approach because the scale of proteins is above nanometers. To precise control the locations of small molecules to manipulate protein functions, we exploit synthetic biomolecules as scaffolds.

We construct nanoscaffolds with polyproline peptide as these biomolecules form well-defined polyproline helix II (PPII) structure that has three fold symmetry and 0.9 nm pitch for every three proline residues. By installing chemical handle into proline building block for SPPS and controlling the peptide sequence, small molecule (ligand) location, distance and direction can be controlled at the range of few nanometers.

Many protein receptors appear in oligomers and this is common for lectins. For example, some human lectins use this multivalent capability to recognize pathogens through glycan ligand density. To control ligand presentation in a universal approach, we connect several polyproline helix into a macrocycle. The assembly on polyproline helices can be efficiently carried out on a solid support with CuAAC reaction and further cyclized into macrocycles. As the ligand position on each helix can be controlled by SPPS and the helix assembly is stepwise, the individual ligands can be controlled into asymmetrical pattern. With these glycan ligand patterns, we manipulate the selective binding to to protein oligomers this strategy can be considered a general solution to the cross-reactivity problem of carbohydrate-protein interaction.