DNA strand scission by neocarzinostatin: molecular recognition process responsible for site-specificity.
A series of hexanucleotides possessing A-T, G-C, inosine (I)-C and 2-aminoadenine (ANH2)-T base pairs at 5'-side of the target thymine were prepared and their selectivity for C-5' and C4' oxidation in the NCS-mediated degradation was investigated. Quantitative product analysis indicated that preferential C5' oxidation of deoxyribose moiety of the target T occurs at -5'-AT- and 5'-IT- sites, whereas C5' and C4' oxidation occurs competitively at T of -5'-GT- and -5'-ANH2T- sites. Based on the experimental results, an intercalation model that permits competitive hydrogen abstraction from C5' and C4' of deoxyribose moiety has been proposed.
Sugiyama
H
H
Department of Synthetic Chemistry, Faculty of Engineering, Kyoto University, Japan.
Fujiwara
T
T
Kawabata
H
H
Saito
I
I
Hirayama
N
N
Yoda
N
N
D001483:Base Sequence; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D006860:Hydrogen Bonding; D006900:Hydroxylation; D008958:Models, Molecular; D015394:Molecular Structure; D009711:Nucleotides / Q000378:metabolism; D010084:Oxidation-Reduction; D009353:Zinostatin / Q000494:pharmacology*
D009711:Nucleotides; D004247:DNA; D009353:Zinostatin