个人简介

A. B., Bowdoin College, 1987 M. A., Columbia University, 1988 Ph. D., Caltech, 1992 NIH Postdoctoral Fellow, M.I.T., 1992-94

研究领域

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. We are also involved with a collaborative program that integrates a combinatorial genomic technology with structural biology and combinatorial chemistry with Profs. Philip Cunningham (Biological Sciences) and John SantaLucia (Chemistry). These experiments focus on the small ribosomal subunit. The 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.

近期论文

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Sakakibara, Y.; Abeysirigunawardena, S. C.; Duc, A.-C.; Dremann D. N.; Chow, C. S. "Ligand- and pH-Induced Conformational Changes of RNA Domain Helix 69 Revealed by 2-Aminopurine Fluorescence", Angew. Chem. Int. Ed. Engl. 2012, 51, 12095-12098. Sakakibara, Y.; Chow, C. S. "Role of Pseudouridine in Structural Rearrangements of Helix 69 During Bacterial Ribosome Assembly", ACS Chem. Biol. 2012, 7, 871-878. Sakakibara, Y.; Chow, C. S. "Probing Conformational States of Modified Helix 69 in 50S Ribosomes", J. Am. Chem. Soc. 2011, 133, 8396-8399. Asare-Okai, P. N.; Chow, C. S. "A Modified Fluorescent Intercalator Displacement Assay for RNA Ligand Discovery", Anal. Biochem. 2011, 408, 269-276. Lamichhane, T. N.; Abeydeera, N. D.; Duc, A.-C.; Cunningham, P. R.; Chow, C. S. "Selection of Peptides Targeting Helix 31 of Bacterial 16S Ribosomal RNA by Screening M13 Phage-Display Libraries", Molecules 2011, 16, 1211-1239. Li, M.; Duc, A.-C.; Klosi, E.; Pattabiraman, S.; Spaller, M. R.; Chow, C. S. "Selection of Peptides That Target the Aminoacyl-tRNA Site of Bacterial 16S Ribosomal RNA", Biochemistry 2009, 48, 8299-8311. Rijal, K.; Chow, C. S. "A New Role for Cisplatin: Probing Ribosomal RNA Structure", Chem. Commun. 2009, 107-109. Chow, C. S.; Mahto, S. K.; Lamichhane, T. N. "Combined Approaches to Site-Specific Modification of RNA", ACS Chemical Biology 2008, 3, 30-37.