Organic Chemistry and Chemical Biology
New Catalysts and Reactions for Organic Synthesis
Our research objective is to develop new catalytic reactions, and efficient strategies for accessing both natural and synthetic organic molecules for potential applications in drug discovery and chemical biology. Specific areas of interest include transition-metal catalysis, supported organocatalysts and sustainable chemistry.
Small Molecules for Targeting Nucleic Acid Structures
Nucleic acids play important roles in living systems such as storage of genetic information, replication, transcription, and translation. DNA can adopt a variety of secondary structures including G-quadruplex, i-motif, triplex, hairpin etc. Secondary structures formed from RNA (miRNA, HIV-TAR RNA, etc.) are equally important in regulating the expression of proteins, which mediate important biological functions. Therefore, these secondary structures have largely evolved as important drug targets in nucleic acid targeted therapeutics. We are synthesizing a variety of small molecules: natural products and their analogues, peptidomimetics and nucleosides that can selectively recognize secondary nucleic acid structures compared to the double helical DNA. We employ rational design, target-assisted combinatorial chemistry, biophysical chemistry and molecular biology to develop and evaluate new chemical scaffolds that can regulate the structure and function of nucleic acids (DNA and RNA).
Supramolecular Chemistry of Nucleobases
The nucleic acids DNA and RNA are the most interesting bio-polymers, in which the five naturally occurring nucleobases adenine, cytosine, guanine, thymine and uracil are involved in H-bonding interactions. The double-stranded DNA/RNA structures are mainly based on the complementary Watson–Crick H-bonding pairings of guanine with cytosine, and adenine with thymine (or uracil), while the G-rich DNA/RNA strands fold to form G-quadruplex structures that contain Hoogsteen H-bonding assembly of four guanines. Our current research is focused on the synthesis and self-assembly of nucleobase derivatives to generate bio-inspired nano-structures, hydrogels and transmembrane ion channels.