Our aim is to understand the structure-function relationship of modified nucleosides and nucleotides in nucleic acids. Our objective is to establish by x-ray diffraction techniques the three dimensional structures of mRNA caps, oligo 2-5's that are the signal of dsRNA in interferon treated cells and of short pieces of oligonucleotides with and without mutagens and carcinogens intercalated or covalently bound. The stereochemistry of 2'-5' and 5'-5' phosphodiester links will be studied and will be compared with the stereochemistry of 3'-5' links.
Our aim i s to understand why 3'-5' phosphodiester bonds and not the 2'-5' phosphodiester bonds are actually used in all genetic information transfer though the 2'-5' links are formed more readily. The conformational flexibility of 5'-5' links will be explored using our structural studies on NAD (nicotinamide adenine dinucleotide) and its several derivatives like NADH, NADP, NADPH and their analogs. Oligonucleotides of varying lengths and sequences are being synthesized and studied using x-ray diffraction. Stereochemical studies on oligonucleotides modified with carcinogens and of cis-synphotodimer of thymidylyl (3'-5')thymidine are in progress.

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National Institute of General Medical Sciences (NIGMS)
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Biophysics and Biophysical Chemistry A Study Section (BBCA)
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Roswell Park Cancer Institute Corp
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Soni, Sunil Dutta; Srikrishnan, Thamarapu (2004) Crystal structure and conformation of 5-fluorouridine: conformational preferences for 5-fluorinated pyranosides. Nucleosides Nucleotides Nucleic Acids 23:1779-95
Stokes, David M; Paul, Brajeswar; Alderfer, James L et al. (2002) Synthesis, structure, and conformation of anti-tumor agents in the solid and solution states: hydroxyl derivatives of Ftorafur. Nucleosides Nucleotides Nucleic Acids 21:863-82
Chaturvedi, S; Parthasarathy, R (1993) Synthesis and immunological properties of bombesin analogs. Int J Pept Protein Res 41:333-7
Parthasarathy, R; Go, K; Chaturvedi, S (1993) Helix-forming tendencies of amino acids depend on their sequence contexts: tripeptides AFG and FAG show incipient beta-bulge formation in their crystal structures. Biopolymers 33:163-71
Go, K; Chaturvedi, S; Parthasarathy, R (1992) Helix-forming tendencies of amino acids depend on the restrictions of side-chain rotamer conformations: crystal structure of the tripeptide GAI in two crystalline forms. Biopolymers 32:107-17
Kim, H; Parthasarathy, R (1991) Structure and conformation of 5-bromo-2',3'-dideoxyuridine. Acta Crystallogr C 47 ( Pt 9):1892-5
Srikrishnan, T; Parthasarathy, R (1990) Structure of N-methylnicotinamide. Acta Crystallogr C 46 ( Pt 9):1723-5
Parthasarathy, R; Chaturvedi, S; Go, K (1990) Design of crystalline helices of short oligopeptides as a possible model for nucleation of alpha-helix: role of water molecules in stabilizing helices. Proc Natl Acad Sci U S A 87:871-5
Srikrishnan, T; Chowdhary, M S; Matta, K L (1989) Crystal and molecular structure of methyl O-alpha-D-manno-pyranosyl-(1----2)-alpha-D-mannopyranoside. Carbohydr Res 186:167-75
Parthasarathy, R; Kim, H (1988) Conformation and sandwiching of bases by azido groups in the crystal structure of 3'-azido-3'-deoxy-thymidine (AZT), an antiviral agent that inhibits HIV reverse transcriptase. Biochem Biophys Res Commun 152:351-8

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