Christine S. Chow (aa2178)

Chemistry

Chem 479

Nucleic acid, bioorganic and bioinorganic chemistry

One of the long-term objectives of our research program is to understand the structural and functional roles of modified nucleosides in RNA. Although over 100 modifications and their locations in tRNAs and rRNA molecules have been identified, many questions still exist regarding the individual contributions of these modifications to RNA structure and function. Research in our group focuses on methodologies for the site-specific incorporation of modified nucleosides into RNA. The effects of modified bases on the structure and stability of ribonucleotide fragments (model RNAs) are being examined by a variety of biophysical methods. To better understand RNA dynamics and the influence of modified nucleotides, a major focus of our work is helix 69 of 23S rRNA, which contains three pseudouridine residues in its loop region. Ribosome-probing experiments are used to examine specific base accessibilities and individual nucleotide conformations that are influenced by the presence of modifications. We are also using inorganic molecules to examine nucleic acid structure. In particular, we employ platinum(II) complexes to probe the structures of large ribosomal RNA systems.

Studies in our laboratory have also focused on the characterization of drug-RNA interactions in solution using fluorescence spectroscopy and other biophysical techniques, such as mass spectrometry. RNAs that can interact antibiotics, metal ions, peptides, and small organic molecules have been synthesized. Fluorescence spectroscopy and electrospray ionization mass spectrometry methods are used to screen for improved RNA-binding ligands that can be further developed into potential antibiotics.

Our long-term goal is to develop new anti-infectives that address the issue of antibiotic resistance. Interactions of drug leads with their rRNA targets are characterized using a variety of biophysical methods to identify compounds with the highest binding affinity and specificity.

• NIH 4DP7OD018427-04, Wayne State University - Broadening Experiences in Scientific Training (BEST) (PI: Mathur), 2013–2019
• NSF CHE 1904754 (PI: Bryant-Friedrich), 2019–2022
• NIH T32GM139807, IMSD at Wayne State University graduate training program (MPI: Lanier, Chow, and Cote), 2/2021–1/2026
• NIH T32GM142519, Chemistry Biology Interface graduate training program (MPI: Pflum and Chow), 7/2021–6/2026

• Jiang, J.; Aduri, R.; Chow, C. S.; SantaLucia, J., Jr. "Structure Modulation of Helix 69 from Escherichia coli 23S Ribosomal RNA by Pseudouridylations", Nucleic Acids Res. 2014, 42, 3971–3981
• Rijal, K.; Bao, X.; Chow, C. S. "Amino Acid-Linked Platinum(II) Analogues Have Altered Specificity for RNA Compared to Cisplatin", Chem. Comm. 2014, 50, 3918–3920
• Jiang, J.; Kharel, D. N.; Chow, C. S. "Modulation of Conformational Changes in Helix 69 Mutants by Pseudouridine Modifications", Biophys. Chem. 2015, 200-201, 48–55
• Dedduwa-Mudalige, G. N. P.; Chow, C. S. "Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins",  Int. J. Mol. Sci. 2015, 16, 21392–21409
• He, C. C.; Kimutai, B.; Bao, X.; Hamlow, L.; Zhu, Y.; Strobehn, S. F.; Gao, J.; Berden, G.; Oomens, J.; Chow, C. S.; Rodgers, M. T. "Evaluation of Hybrid Theoretical Approaches for Structural Determination of a Glycine-Linked Cisplatin Derivative via IRMPD Action Spectroscopy", J. Phys. Chem A. 2015, 119, 10980–10987
• Jiang, J.; Seo, H.; Chow, C. S. "Post-transcriptional Modifications Modulate rRNA Structure and Ligand Interactions", Accts Chem. Res. 2016, 49, 893–901
• Dremann, D. N.; Chow, C. S. "The Development of Peptide Ligands that Target Helix 69 rRNA of Bacterial Ribosomes", Bioorg. Med. Chem. 2016, 24, 4486–4491. 
• Sakakibara, Y.; Chow, C. S. "Pseudouridine Modifications Influence Binding of Aminoglycosides to Helix 69 of Bacterial Ribosomes", Org. Biomol. Chem. 2017, 15, 8535–8543
• Waduge, P.; Sakakibara, Y.; Chow, C. S. "Chemical Probing for Examining the Structure of Modified RNAs and Ligands to RNA", Methods 2019, 156, 110–120
• Dremann, D. N.; Chow, C. S. "The Use of Electrospray Ionization to Monitor RNA-Ligand Interactions", Methods Enzymol. 2019, 623, 315–337
• Waduge, P.; Sati, G. C.; Crich, D.; Chow, C. S. "Use of a Fluorescence Assay to Determine Relative Affinities of Semisynthetic Aminoglycosides to Small RNAs Representing Bacterial and Mitochondrial A Sites", Bioorg. Med. Chem. 2019, 27, 1115121. 
• Muthunayake, N. S.; Islam, R.; Inutan, E. D.; Colangelo, W.; Trimpin, S.; Cunningham, P. R.; Chow, C. S. “Expression and in Vivo Characterization of the Antimicrobial Peptide Oncocin and Variants Binding to Ribosomes”, Biochemistry 2020, 59, 3380–3391
• Jones, E. L.; Mlotkowski, A. J.; Hebert, S. P.; Schlegel, H. B.; Chow, C. S. "Calculations of pKa Values for a Series of Naturally Occurring Modified Nucleobases", J. Phys. Chem. A. 2022, 126, 1518–1529

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