Showing papers by "Seog K. Kim published in 1991"
TL;DR: The conformations of covalent adducts derived from the binding of the highly tumorigenic stereoisomer (+)-trans- 7,8-dihydroxy-anti-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyren e and its nontumorigenic (-)-anti-BPDE isomer were investigated by employing UV absorbance and linear dichroism methods.
Abstract: The conformations of covalent adducts derived from the binding of the highly tumorigenic stereoisomer (+)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyren e [(+)-anti-BPDE] and its nontumorigenic (-)-anti-BPDE isomer with poly[(dG).(dC)], poly[(dG-dC).(dG-dC)], poly[(dT-dC).(dG-dA)], and poly[(dA-dC).(dG-dT)] were investigated by employing UV absorbance and linear dichroism methods. The degrees of orientation of the BPDE residues (bound covalently to N2 of deoxyguanosine), relative to the DNA bases, are most pronounced in the alternating and nonalternating (dG).(dC) polymers and decrease in polymers with neighboring dA.dT base pairs. The tumorigenic (+)-anti-BPDE isomer gives rise predominantly to external (solvent-exposed) site II adducts, while the (-)-enantiomer gives rise predominantly to site I adducts with significant carcinogen-nucleoside interactions. In the mixed (dA-dC).(dG-dT) and (dT-dC).(dG-dA) copolymers, the (+)-anti-BPDE isomer also binds predominantly to N2 of deoxyguanosine, but the adducts are weakly oriented with respect to the DNA bases. The incidence of site II adducts is considerably reduced as compared to the (dG).(dC) and (dG-dC).(dG-dC) polymers, and there is a greater proportion of site I adducts; the presence of a significant proportion of unordered adduct forms is also suggested from the diffuseness and broadness of the absorption spectra in the dA.dT base pair containing polymers. The preference of formation of site II adducts in dG-rich sequences in the case of the biologically highly active (+)-anti-BPDE isomer is discussed in terms of the known binding and mutation spectra.
18 citations
TL;DR: Fluorescence spectra of the trans and cis isomers of the adduct formed from guanosine monophosphate and theAdducts of d(ATATGTATA) are used to assign the stereochemistry of the two major DNA adducts as trans-N2-dG moieties which occupy two different DNA sites.
Abstract: A recently developed methodology [Jankowiak, R., Lu, P., Small, G. J., and Geacintov, N. E. (1990) Chem. Res. Toxicol. 3, 39-46], which combines fluorescence line narrowing spectroscopy at 4.2 K with non-line-narrowed (S2----S0 laser excitation) fluorescence spectroscopy at 77 K and fluorescence quenching, is used to characterize adducts formed from (+)-anti-BPDE and the alternating copolymers poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT), the nonalternating poly (dG).poly(dC), single-strand poly(dG), and the oligonucleotide d(ATATGTATA). Detailed comparisons of the fluorescence spectra and quenching (with acrylamide) of the properties of the adducts with those of (+)-anti-BPDE-DNA adducts are made. Fluorescence spectra of the trans and cis isomers of the adduct formed from guanosine monophosphate and the adducts of d(ATATGTATA) are used to assign the stereochemistry of the two major DNA adducts as trans-N2-dG moieties which occupy two different DNA sites. Evidence for the existence of minor cis-type guanine adducts is provided. Finally, a fourth type of DNA adduct (minor) is identified and assigned as trans-N6-dA.
16 citations
TL;DR: H-1 NMR studies of the interactions with the self-complementary oligonucleotide d(CGCGATC GCG)2 indicate that both enantiomers bind into the minor groove of the central AT-TA region, but with a rapid exchange between the bound and free states.
Abstract: Despite extensive study of DNA interaction with propeller-shaped metal complexes, such as the DELTA and LAMBDA enantiomers of [Ru(1,10-phenanthroline)3]2+, the basis for their enantioselectivity, and even their binding modes, are not yet fully understood. H-1 NMR studies of the interactions with the self-complementary oligonucleotide d(CGCGATCGCG)2 indicate that both enantiomers bind into the minor groove of the central AT-TA region, but with a rapid exchange between the bound and free states. Flow linear dichroism (FLD) and circular dichroism (CD) show different binding geometries for the two enantiomers. These two geometries are found in natural DNA as well as in a number of different B form polynucleotides, virtually independent of base composition and of methylation. The DNA interaction with the [Ru(1,10-phenanthroline)3]2+ complexes will be reconsidered in the light of NMR, FLD, CD and fluorescence results.
13 citations