Abstract:
The Luk's research group advances at the interface of chemical and biological catalysis. It can be broadly divided into two branches:
(1) Designing host-guest systems for organocatalysis has gained increasing interest in recent years. Here, we have adapted the streptavidin-biotin technology to investigate the use of a protein host for secondary amine organocatalysis. Different from traditional small-molecule organocatalytic systems, enantiomeric enrichment of the supramolecular system is completely controlled by the protein host. Mechanistic investigations by X-ray crystallography, computational analysis, reaction scope and mutagenesis studies have revealed catalytically important residues and the importance of the subunit interface in catalysis. Together, this work illustrates that proteins can be an excellent supramolecular host for driving stereoselective secondary amine organocatalysis.
(2) Provided that peptides and proteins have increasing importance in applied research, e.g. protein therapeutics, peptides as drugs and insecticides. Tremendous efforts have been made to improve the techniques surrounding peptide and protein modifications. Enzymes, including transpeptidase, present as ideal tools, because they are catalytically efficient and can be readily prepared in most laboratories. Nevertheless, technical issues including reversibility and peptide solubility have not been addressed. Based on our mechanistic investigations, we will present our approaches to create (A) a peptide ligation system that enables high-yielding protein modification, and (B) a plant-inspired technology for peptide cyclization.
Bibliography
2015-present: University Research Fellow, Cardiff University, Cardiff, UK
2012-2015 Research Associate, School of Chemistry, Cardiff University, Cardiff, U.K. PI: Professor Rudolf K. Allemann
2010-2011 Postdoctoral Scholar, Department of Molecular Biology, University of Chicago, Chicago, U.S.A. PI: Professor Stephen B. H. Kent
2004-2010 Ph. D. Candidate, Department of Chemistry, University of British Columbia, Vancouver, Canada. PI: Professor Martin E. Tanner