3′-Intercalation of a N²-dG 1R-trans-anti-Benzo[c]phenanthrene DNA Adduct in an Iterated (CG)₃ Repeat

Abstract

The conformation of the 1R,2S,3R,4S-benzo [c]phenanthrene-N 2 -dG adduct, arising from trans opening of the (+)-1S,2R,3R,4S-anti-benzo[c]phenanthrene diol epoxide, was examined in 5′-d (ATCGCXCG-GCATG)-3′·5′-d(CATGCCGCGCGAT)-3′, where X = 1R,2S,3R,4S-B[c]P-N 2 -dG. This duplex, derived from the hisD3052 frameshift tester strain of Salmonella typhimurium, contains a (CG) 3 iterated repeat, a hotspot for frameshift mutagenesis. NMR experiments showed a disconnection in sequential NOE connectivity between X 4 and C 5 , and in the complementary strand, they showed another disconnection between G 18 and C 19 . In the imino region of the 1 H NMR spectrum, a resonance was observed at the adducted base pair X

Elucidating the intercalation of methylated 1,10-phenanthroline with DNA: the important weight of the CH/H interactions and the selectivity of CH/π and CH/n interactions

“…In order to study the intercalation of methylated phen derivatives the so-called ring models 31 have been considered. We built these ring models from the 32 crystal structure taken from the Protein Data Bank (PDB). Starting from this structure, the (1 R-trans -antibenzo[ c ]phenanthrene) ligand between the bps of DNA was removed and the N2 of the guanine was saturated.…”

Repair-Resistant DNA Lesions

“…Analyses of structural features of many modified nucleobases by solution NMR methods 71,82,98,108,124,125,134−137 have yielded a wealth of information on their conformations and the distortions of the local DNA structure that they cause.…”

Structure-Based DNA-Targeting Strategies with Small Molecule Ligands for Drug Discovery

“…Likewise, recently several other minor groove binders or intercalating agents have also been covalently linked with DNA at specific positions . It was revealed that this covalent bonding can greatly stabilize DNA–ligand interactions, and the duplex conformation can also be altered.…”

“…148 Likewise, recently several other minor groove binders or intercalating agents have also been covalently linked with DNA at specific positions. 33,149 It was revealed that this covalent bonding can greatly stabilize DNA-ligand interactions, and the duplex conformation can also be altered. More importantly, since most molecules only have weak preference for a specific sequence and binding to several alternative sites often happens, these combination modes thus provide a convenient way of "site-specific DNA-targeting."…”