Welcome to Chow Lab Research Exploring the RNA World, One Modification at a Time
"All for One and One for All "
Our Approach
Project 1 - Synthesis of the 6-O-DPC-2-N-methylguanosine (m2G) nucleoside and the corresponding 5’-O-DMT-2’-O-TOM-protected 6-O-DPC-2-N-methylguanosine phosphoramidite [DPC, diphenyl carbamoyl; DMT, 4, 4’-dimethoxytrityl; TOM, [(triisopropylsilyl)oxy]methyl].
Project 2 - Syntheses of acp3m1Ψ and corresponding 5’-O-DMT-2’-O-TBS-protected acp3m1Ψ phosphoramidite
Project 3- Exploring the significance of those modifications in H31 by using various biophysical approaches
One of the long term objectives in our group research is to understand the roles of the modified nucleotides present in ribosomal RNA. My research project involves the use of bioorganic and biophysical approaches to help us better understand the roles of methylated analogs.
Primarily, my research focuses on the characterization of the effects of modified nucleotides present in helix 31 (H31) of 16S ribosomal RNA. In particular, I have worked on the synthesis of the 6-O-DPC-2-N-methylguanosine (m2G) nucleoside and the corresponding 5’-O-DMT-2’-O-TOM-protected 6-O-DPC-2-N-methylguanosine phosphoramidite [DPC, diphenyl carbamoyl; DMT, 4, 4’-dimethoxytrityl; TOM, [(triisopropylsilyl)oxy]methyl]. Availability of the amidite allowed incorporation of m2G into specific RNA regions of interest. The two methylated bases, m2G966 and m5C967, occur at the same locus as the hypermodified nucleotide 1-methyl-3-(3-amino-3-carboxypropyl) pseudouridine (acp3m1Ψ) in H. sapiens. The syntheses of acp3m1Ψ and corresponding 5’-O-DMT-2’-O-TBS-protected acp3m1Ψ phosphoramidite will allow the selective incorporation of acp3m1Ψ into H. sapiens RNA helices. I am exploring the significance of those modifications in H31 by using various biophysical approaches.My ultimate goal is to discover a ligand/s that can bind only to this region of E. coli 16S rRNA, and utilize helix 31 as a possible drug target in the ribosome. Supported by NIH GM076794 (PI: A. Grow).
