Structural characterization of 1,N2-ethenodeoxyguanosine in the dodecamer 5'-CGCATethenoGGAATCC-3'

TOXI 110

Ganesh Shanmugam, ganesh.shanmugam@vanderbilt.edu1, Ivan D. Kozekov, ivan.kozekov@vanderbilt.edu2, F. Peter Guengerich, f.guengerich@vanderbilt.edu3, Carmelo J. Rizzo, c.j.rizzo@vanderbilt.edu2, and Michael P. Stone, michael.p.stone@vanderbilt.edu2. (1) Department of Chemistry, Vanderbilt University, VU Station B Box 351822, Nashville, TN 37235, (2) Department of Chemistry, Center in Molecular Toxicology and the Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN 37235, (3) Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University, 642 Robinson Research Building, 23rd and Pierce Aves, Nashville, TN 37232
The structure of the 1,N2-ethenodG adduct, arising from the reaction of vinyl chloride with dG, was determined in 5'-d(CGCATethenoGGAATCC)-3'•5'-d(GGATTCCATGCG)-3' using NMR spectroscopy. The 1,N2-ethenodG adduct shifted the conformational equilibrium about the glycosyl bond at the adducted dG. At neutral pH, a mixture of the syn and anti conformations existed. The 1,N2-ethenodG adduct adopted the syn conformation under acidic conditions, whereas, it adopted the anti conformation under basic conditions. The structures of each of these conformations of the adduct and their effects upon the base pair arrangement of the 1,N2-ethenodG:dC pair and its neighboring base pairs will be discussed. The NMR results will be compared with crystal structures of primer template complexes site-specifically modified with the 1,N2-ethenodG adduct in the presence of the Sulfolobus solfataricus DNA Polymerase Dpo4. Supported by NIH grants ES-05355 (M.P.S. and C.J.R.) and ES-010375 (F.P.G.).
 

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007