Monoalkylation of DNA by reductively activated FR66979

Bioorganic and Medicinal Chemistry

Volumn 8, Issue 1, 2000, Pages 173-179

  Paz, Manuel M ^a   Sigurdsson, Snorri Th ^a   Hopkins, Paul B ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Antibiotics; Antitumor compds; DNA; Nucleic acids

Indexed keywords

ANTINEOPLASTIC AGENT; DEOXYGUANOSINE; DNA; DOUBLE STRANDED DNA; MITOMYCIN C;

ALKYLATION; ARTICLE; CHEMICAL REACTION; CROSS LINKING; DENATURATION; ELECTROPHORETIC MOBILITY;

ALKYLATION; BASE SEQUENCE; DNA; DNA ADDUCTS; DNA, SINGLE-STRANDED; KINETICS; OXAZINES; SULFHYDRYL COMPOUNDS;

EID: 0034007670     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0968-0896(99)00270-9     Document Type: Article

References (15)

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11. To explore the possibility that the isolated monoadducts were intermediates on the interstrand cross-linking pathway, the FR66979-modified DNA monoadduct 7 was annealed to its dG-containing complementary strand and incubated for 20 h at 25 °C. The analysis of the mixtures by DPAGE showed the formation of cross-linked DNA (10% yield) with the same mobility as the one obtained from treatment of duplex I with FR66979 (data not shown). The relatively low yield of cross-linking indicated that the monoadducts were not efficiently cross-linked. Further indication that these monoadducts were not on the major cross-linking pathway was provided by the observation that increased amounts of DTT, in a DTT-activated FR66979 cross-linking of duplex I, decreased the amount of interstrand cross-links, relative to that of the monoadducts (data not shown). The interstrand cross-linked DNA, obtained by incubation of monoadduct 7 with its complementary strand, was enzymatically digested and analyzed by HPLC (data not shown). The HPLC chromatogram revealed that dG was absent and instead, a strongly retained peak was observed which coeluted with an authentic sample of the bisadduct 6. This provided further evidence for conjugation of the monoadduct to N2 of dG. However, it cannot be conclusively ruled out that this cross-linked material originated from a minor component of the monoadduct mixture (only 10% yield of cross-linking) and that the majority of the monoadducts were connected to a site different than N2 of dG.
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