Chemical Biology and Bioinorganic Chemistry
We work at the interface of chemistry and biology. We investigate the role of inorganic elements and small molecules in biological systems. We leverage the principles of biochemistry, organic synthesis, inorganic chemistry, and biophysics to understand the intricate interactions between biological molecules and metal ions or other small molecules.
Functional model of metalloenzymes
Metalloenzymes are enzymes that contain metal ions at their active sites, which play a crucial role in catalyzing various chemical reactions in living organisms. These metal ions impart unique reactivity, selectivity, and efficiency to the enzymes, making them fascinating targets for biomimetic research. We aim to construct synthetic metalloenzymes by incorporating metal ions into synthetic biomimetic scaffolds or artificial protein frameworks. These synthetic constructs can mimic the reactivity and selectivity of natural metalloenzymes while offering the potential for fine-tuning and customization of their reactivity and selectivity. Currently, we are developing a chemical model for an enzyme called TET, ten-eleven translocation enzyme. This enzyme is responsible for oxidizing the methyl group of the methylated cytosine (mC) residue in DNA. The TET enzyme is a Fe-containing enzyme, and the Fe centre is coordinated to two histidine residues, one glutamate residue and an alpha-ketoglutarate cofactor. The TET enzyme iteratively oxidizes the methyl group in cytosine residue to hydroxy (5-hmC), formyl (5-fC), and carboxy (5-caC), respectively. This stepwise activation of strong C-H bond at ambient conditions is not straightforward. Also, the distribution of oxidized 5-mC derivatives are not uniform, meaning the TET enzyme has different substrate selectivity. We are trying to understand all these unsolved mistry of the TET enzyme by designing small molecule-based synthetic models.
Controlling metal homeostasis
The concentration of each and every essential elements in the biological system are tightly regulated. Metals, especially transition metals are not an exception in this regard. Metal ions play vital roles in numerous biological processes, ranging from enzymatic catalysis and electron transfer to DNA repair and gene regulation. Maintaining the proper balance of metal ions within cells is essential for their optimal functioning, and disruptions in metal homeostasis have been linked to various disease states. Our group aims to develop small molecules that can interact with specific metal ions in biological systems. By selectively binding to these metal ions, these molecules can modulate their concentration, distribution, and reactivity, allowing precise control over metal homeostasis.
We are trying to harness the power of light and small molecules to precisely manipulate and regulate various biological processes. Our research focuses on developing innovative strategies that combine light-responsive small molecules with biological systems, enabling unprecedented control over cellular functions with spatial and temporal precision. By leveraging the power of light and small molecules, we seek to provide researchers and clinicians with unprecedented control and manipulation capabilities, opening new frontiers in biology, medicine, and biotechnology.