Distortion after monofunctional alkylation by mitomycin C of a dodecamer containing its major binding site.
The structural distortions of the duplex dodecamer d(ATTAACGTTAAT)2 monofunctionally alkylated by mitomycin C have been studied by the use of chemical probes reactivity and resonance Raman spectroscopy. This sequence contains the 5'-ACGT sequence for which mitomycin C was determined to present the best affinity (S. Kumar, R. Lipman, and M. Tomasz, Biochemistry 31, 1399 (1992)). Raman spectroscopy as well as osmium tetroxyde reactivity indicate that the distortion of the double helix structure is located around the central CG bases. Mitomycin C reacts exclusively with the 2-amino group of guanine and this binding does not disrupt the inter bases H-bonds, as indicated by chloroacetaldehyde reactivity. Although resonance Raman spectroscopy does not allow the handedness of the monoalkylated CG/GC sequence to be determined, it indicates a similarity between the base stacking and that which would be observed for alternating purine/pyrimidine sequences at high salt concentration.
Berthelier
V
V
L.P.C.B. (CNRS UA 198), Institut Curie, Paris.
Laigle
A
A
Jollès
B
B
Chinsky
L
L
D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000737:chemistry; D000478:Alkylation; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000187:drug effects*; D015342:DNA Probes / Q000737:chemistry; D006147:Guanine / Q000737:chemistry; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000737:chemistry; D016685:Mitomycin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D017892:Osmium Compounds / Q000737:chemistry; D013059:Spectrum Analysis, Raman
D015342:DNA Probes; D006898:Hydroxylamines; D017892:Osmium Compounds; D019811:Hydroxylamine; D016685:Mitomycin; D006147:Guanine; D004247:DNA; C004656:chloroacetaldehyde; D000079:Acetaldehyde