Rapid and Efficient Hybridization-Triggered Crosslinking Within a DNA Duplex by an Oligodeoxyribonucleotide Bearing a Conjugated Cyclopropapyrroloindole | Zendy

E. A. Lukhtanov | Zendy; M. A. Podyminogin | Zendy; Igor V. Kutyavin | Zendy; Rich B. Meyer | Zendy; Howard Gamper | Zendy

Open Access

Rapid and Efficient Hybridization-Triggered Crosslinking Within a DNA Duplex by an Oligodeoxyribonucleotide Bearing a Conjugated Cyclopropapyrroloindole

Author(s) -

E. A. Lukhtanov,

M. A. Podyminogin,

Igor V. Kutyavin,

Rich B. Meyer,

Howard Gamper

Publication year - 1996

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/24.4.683

Subject(s) - biology , dna , duplex (building) , conjugate , oligonucleotide , moiety , microbiology and biotechnology , coding strand , transcription (linguistics) , stereochemistry , biochemistry , chemistry , polymerase , mathematical analysis , linguistics , philosophy , mathematics

The antitumor antibiotic CC-1065 binds in the minor groove of double-stranded DNA, and the cyclopropapyrroloindole (CPI) subunit of the drug alkylates adjacent adenines at their N-3 position. We have attached racemic CPI to oligodeoxyribonucleotides (ODNs) via a terminal phosphorothioate at either the 3'- or 5'-end of the ODNs. These conjugates were remarkably stable in aqueous solution at neutral pH even in the presence of strong nucleophiles. When a 3'-CPI-ODN conjugate was hybridized to a complementary DNA strand at 37 degrees C, the CPI moiety alkylated nearby adenine bases of the complement efficiently and rapidly, with a half-life of a few minutes. The 4'-CPR- ODN conjugate showed very little reactivity within the duplex. CPI-ODN conjugates should be highly effective sequence-specific inhibitors of single-stranded viral DNA replication or gene selective inhibitors of transcription initiation.

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