title: Conformational changes of the phenyl and naphthyl isocyanate-DNA adducts during DNA replication and by minor groove binding molecules.
abstract: DNA lesions produced by aromatic isocyanates have an extra bulky group on the nucleotide bases, with the capability of forming stacking interaction within a DNA helix. In this work, we investigated the conformation of the 2'-deoxyadenosine and 2'-deoxycytidine derivatives tethering a phenyl or naphthyl group, introduced in a DNA duplex. The chemical modification experiments using KMnO4 and 1-cyclohexyl-3 -(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate have shown that the 2'-deoxycytidine lesions form the base pair with guanine while the 2'-deoxyadenosine lesions have less ability of forming the base pair with thymine in solution. Nevertheless, the kinetic analysis shows that these DNA lesions are compatible with DNA ligase and DNA polymerase reactions, as much as natural DNA bases. We suggest that the adduct lesions have a capability of adopting dual conformations, depending on the difference in their interaction energies between stacking of the attached aromatic group and base pairing through hydrogen bonds. It is also presented that the attached aromatic groups change their orientation by interacting with the minor groove binding netropsin, distamycin and synthetic polyamide. The nucleotide derivatives would be useful for enhancing the phenotypic diversity of DNA molecules and for exploring new non-natural nucleotides.
authors.affiliation: Department of Nanobiochemistry, Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan, Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan, Department of Chemistry, Faculty of Science and Engineering, Konan University, 8-9-1, Okamoto, Higashinada-ku, Kobe, 658-8501, Japan, Molecular Engineering Institute (MEI), Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka, 820-8555, Japan and Department of Environmental and Biological Chemistry, Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka, 820-8555, Japan.
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Nakano
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Uotani
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Hirohito
authors.initials: H
authors.lastname: Oka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujii
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugimoto
mesh_terms: D018736:DNA Adducts / Q000737:chemistry*; D011088:DNA Ligases / Q000378:metabolism; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003839:Deoxyadenosines / Q000737:chemistry*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry; D004214:Distamycins / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D009429:Netropsin / Q000737:chemistry; D009690:Nucleic Acid Conformation; D013941:Thymine / Q000737:chemistry
chemical_list: D018736:DNA Adducts; D003839:Deoxyadenosines; D004214:Distamycins; C507010:N6-(N'-naphthylcarbamoyl)-2'-deoxyadenosine; C507009:N6-(N'-phenylcarbamoyl)-2'-deoxyadenosine; D003841:Deoxycytidine; D006147:Guanine; D009429:Netropsin; C030000:stallimycin; D004259:DNA-Directed DNA Polymerase; D011088:DNA Ligases; D013941:Thymine