Our research covers broad interests in bioorganic chemistry with a focus on synthesis and problems of biomedical significance at the interface of chemistry and biology. More specifically, our research group is interested in the design of (1) small molecule codes for sequence- and/or secondary structure-specific RNA recognition, (2) functional foldamers (organic oligomers) to mimic the structures and functions of proteins and (3) nanoparticle drug delivery systems.

SMALL MOLECULE CODES FOR SEQUENCE- AND/OR SITE-SPECIFIC RECOGNITION OF RNA:

Traditionally, protein products of genes have been the targets in drug discovery while the intermediary RNA gene products have remained largely unexplored. Considering that 86-90% of the proteins encoded by the ~35,000 human genes are estimated to be non-drugable, targeting RNA may provide an enormous advantage in drug discovery efforts compared with targeting proteins. However, unusual folding patterns of RNA to complicated three-dimensional structures make it a formidable task to custom design RNA binding molecules. More recent studies provided important insights on RNA recognition by aminoglycosides in molecular level through X-ray crystal structures of several aminoglycosides complexed to the 30S ribosomal particle or an A-site oligonucleotide. Aminoglycosides are naturally occurring antibiotics known to bind to various RNAs. Based on the crystal structures, libraries of novel RNA binding molecules will be constructed through structure-based rational design of novel structural analogs of 2-deoxystreptamine (2-DOS), the most conserved RNA recognition subunit among aminoglycosides. The long-term goal of this research is to better understand the underlying principles of RNA recognition process and to develop small molecule codes for specific RNA recognition therefore to control cellular processes in RNA level. (For a review, see Drug Discovery Today 2003, 8, 297-306)

FUNCTIONAL FOLDAMERS TO MIMIC STREUCTURES AND FUNCTIONS OF PROTEINS:

Proteins fold into an array of three-dimensional structures through non-covalent interactions encoded in their primary structure, resulting in numerous functions in the living organisms. Therefore, deeper insight into the folding principles of proteins has been of a great interest to scientists. As such, novel synthetic oligomers capable of mimicking the structures and functions of proteins, so called foldamers, have received much attention recently. In this research, we design foldamers with both a catalytic activity and a functional switch in an effort to mimic protein structures and functions. (For a review, see Eur. J. Org. Chem. 2004, 17-29)

NANOPARTICLE DRUG DELIVERY SYSTEMS:

Nanoscale carriers have received considerable interest for delivery of small organic molecular drugs, proteins, genes and imaging contrast agents. They conceptually protect the active ingredients encapsulated within the particle periphery from untimely metabolic stresses in vivo and provide a means of targeted delivery.

Block ionomers have been recognized as a potential drug delivery system for several decades due to their capability to form well-characterized core-shell micelles. However, their application in drug delivery is still considered inadequate due to instability of the micelle structures and lack of targeting capability. Therefore, strategies will be applied to enhance structural stability of the micelle structure and functionalize surface of the block ionomers for targeted drug delivery. In addition, development of ultrafine sized nanoparticles with high monodispersity will be explored. (For a review on nanoparticle drug delivery, see Science 2004, 303, 1818-1822)