title: Nucleotide sequence specificity in DNA cleavage caused by dihydropyrazines, a new type of DNA strand-cleaving agent.
abstract: The specificity of the nucleotide sequence of DNA strand cleavage sites produced by dihydropyrazines, a new type of DNA strand-cleaving agent, was studied. Biotin-5'-end-labeled PCR-amplified DNA restriction fragments of different defined nucleotide sequences were prepared from plasmid pBR322, and reacted with dihydropyrazines in the presence of Cu2+. After being heated with aqueous piperidine, the DNA products were analyzed on polyacrylamide gels. The most preferentially cleaved sites induced by dihydropyrazines were at purine/pyrimidine-guanine (5' --> 3') sequences. The purine/pyrimidine-adenine, pyrimidine-pyrimidine and purine-pyrimidine (5' --> 3') sequences were more resistant to attack by these dihydropyrazines. The side chains of the dihydropyrazine skeleton greatly affected the DNA strand-cleaving activity, and also, to some extent, the nucleotide sequence-specificity in the DNA strand-cleavage.
authors.affiliation: Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Jonan-ku, Fukuoka 814-0180, Japan. kashige@fukuoka-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Kashige
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: F
authors.initials: F
authors.lastname: Miake
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D001483:Base Sequence; D001710:Biotin / Q000737:chemistry; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D006147:Guanine / Q000494:pharmacology; D008163:Luminescent Measurements; D010957:Plasmids / Q000235:genetics; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011719:Pyrazines; D006147:Guanine; D001710:Biotin; D003300:Copper; D004247:DNA