7,8-Dihydro-8-oxoadenine as a replacement for cytosine in the third strand of triple helices. Triplex formation without hypochromicity.
Oligonucleotides containing thymine and cytosine (or 5-methylcytosine) bases are known to bind to specific homopurine sequences in double-stranded DNA by means of T.AT and C+.GC base triplets. Cytosine in the third strand of such triple helices can be completely replaced by 7,8-dihydro-8-oxoadenine a base which should not require protonation to form base triplets. Experiments using native PAGE and inhibition of triplex-directed photo-cross-linking demonstrate that triplexes with 7,8-dihydro-8-oxoadenine in the third strand are as stable at pH 6.0 as triplexes with 5-methylcytosine. The stability of triplexes with 7,8-dihydro-8-oxoadenine, unlike those with 5-methylcytosine, is not substantially diminished upon raising the pH to 7.4. Surprisingly, triplex formation with an oligonucleotide containing only thymine and 7,8-dihydro-8-oxoadenine was not associated with significant hypochromicity and could not be detected in conventional thermal denaturation experiments.
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Du Pont Merck Pharmaceutical Company, Wilmington, Delware 19880.
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D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D001483:Base Sequence; D003596:Cytosine / Q000737:chemistry*; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D009838:Oligodeoxyribonucleotides; C002992:8-hydroxyadenine; D003596:Cytosine; D000225:Adenine