Abstract:
: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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Lukhtanov EA,Podyminogin MA,Kutyavin IV,Meyer RB,Gamper HBdoi
10.1093/nar/24.4.683subject
Has Abstractpub_date
1996-02-15 00:00:00pages
683-7issue
4eissn
0305-1048issn
1362-4962pii
5j0636journal_volume
24pub_type
杂志文章abstract::Signaling pathways constitute a valuable source of information that allows interpreting the way in which alterations in gene activities affect to particular cell functionalities. There are web tools available that allow viewing and editing pathways, as well as representing experimental data on them. However, few metho...
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