Abstract

The structure of oligodeoxynucleotides modified by the environmental carcinogens benzo(a)pyrene diol epoxide and the carcinogens N-2-(acetylamino)fluorene and N2-(amino)fluorene will be determined by the use of two-dimensional NMR spectroscopy. The distances obtained from NOESY data will be used as restraints in molecular mechanics and molecular dynamics calculations. The three dimensional structures of adducts bound to different sequences will be determined to elucidate the effect of sequence on the structure and dynamics of the adducts. Carcinogen-modified oligodeoxynucleotides will be synthesized containing either codon 12 or codon 61 sequences of the mouse and human c-Ha-ras 1 protooncogenes and the structures determined with covalently attached carcinogens at the guanines which are mutated in activating the oncogenes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM053826-15
Application #
2838624
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1983-08-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
2000-11-30
Support Year
15
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Rochester
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Znosko, Brent M; Kennedy, Scott D; Wille, Pamela C et al. (2004) Structural features and thermodynamics of the J4/5 loop from the Candida albicans and Candida dubliniensis group I introns. Biochemistry 43:15822-37
Znosko, Brent M; Barnes 3rd, Thomas W; Krugh, Thomas R et al. (2003) NMR studies of DNA single strands and DNA:RNA hybrids with and without 1-propynylation at C5 of oligopyrimidines. J Am Chem Soc 125:6090-7
Znosko, Brent M; Burkard, Mark E; Schroeder, Susan J et al. (2002) Sheared Aanti.Aanti base pairs in a destabilizing 2 x 2 internal loop: the NMR structure of 5'(rGGCAAGCCU)2. Biochemistry 41:14969-77
Znosko, Brent M; Burkard, Mark E; Krugh, Thomas R et al. (2002) Molecular recognition in purine-rich internal loops: thermodynamic, structural, and dynamic consequences of purine for adenine substitutions in 5'(rGGCAAGCCU)2. Biochemistry 41:14978-87
Zhang, H; Fountain, M A; Krugh, T R (2001) Structural characterization of a six-nucleotide RNA hairpin loop found in Escherichia coli, r(UUAAGU). Biochemistry 40:9879-86
Chen, X; McDowell, J A; Kierzek, R et al. (2000) Nuclear magnetic resonance spectroscopy and molecular modeling reveal that different hydrogen bonding patterns are possible for G.U pairs: one hydrogen bond for each G.U pair in r(GGCGUGCC)(2) and two for each G.U pair in r(GAGUGCUC)(2). Biochemistry 39:8970-82
Fountain, M A; Serra, M J; Krugh, T R et al. (1996) Structural features of a six-nucleotide RNA hairpin loop found in ribosomal RNA. Biochemistry 35:6539-48