New York, New York, United States
Investigated recognition selectivity of certain residue combinations on cofactor helix of HMG-CoA reductase (HMGR) towards NADH and its phosphorylated analog, NADPH, respectively. Hypothesized that switching residue combinations from two HMGR orthologs would swap selectivity. Conducted mutagenesis to generate residue-swap versions of His-tagged HMGR expression vectors. Expressed and purified HMGRs using Ni-based affinity chromatography. Performed enzyme kinetic assays to determine cofactor preferences and analyzed crystal structures using X-ray synchrotron. Thesis (manuscript ongoing): Studying the Role of the Individual Residues of HMGR Cofactor Helix in Cofactor Specificity Poster presentation: Studying the role of the individual residues of HMGR cofactor helix in cofactor specificity.
Optimized and conducted total synthesis of C14 diisonitrile chalkophore, a natural product involved in copper homeostasis and virulence regulation in Mycobacterium tuberculosis. Helped construct a rapid synthetic platform of chalkophore analogs to investigate their potential as antibacterial agents. Aimed to explore the structure-function relationship of diisonitriles, advancing understanding of their roles in Mycobacterium tuberculosis physiology and virulence. Poster Presentation: Synthesis of C14 diisonitrile natural product from M. tuberculosis.
Synthesized PROTAC version of crosslinked helix dimers (CHD) targeting Myc protein zipper domain. Aimed to bind Myc using PROTAC CHD and degrade it through ubiquitin-proteasome pathway. Made helical monomers through solid-phase peptide synthesis and crosslinked by dibenzyl ether. Explored on-resin and in-solution crosslinking possibilities. Tethered thalidomide to CHD by flexible PEG linker to recruit E3 ligase. Analyzed synthesized peptides and small molecules using MALDI-TOF, NMR, and LCMS. Poster Presentation: Synthesis of helix protein tertiary structure mimic.