The synthesis of 2'-O-methyl G-clamp containing oligonucleotides and their inhibition of the HIV-1 Tat-TAR interaction.
We have synthesised a 2'-O-methyl riboside phosphoramidite derivative of the cytosine analogue 9-(2-aminoethoxy)-phenoxazine ('G-clamp') and successfully incorporated it into a series of small steric blocking 2'-O-methyl oligonucleotides targeting the stem-loop region of HIV-1 TAR RNA. The 'G-clamp' containing oligonucleotides show significant increases in binding to a model TAR RNA system when the 'G-clamp' is positioned opposite the loop region. The oligonucleotides also display dose-dependent inhibition of Tat-dependent transcription of an HIV DNA template in HeLa cell nuclear cell extract.
Holmes
Stephen C
SC
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Gait
Michael J
MJ
D000577:Amides; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives*; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D006367:HeLa Cells; D006801:Humans; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010756:Phosphoric Acids; D013698:Templates, Genetic; D013816:Thermodynamics; D014158:Transcription, Genetic
D000577:Amides; D015696:Gene Products, tat; D009841:Oligonucleotides; D010756:Phosphoric Acids; D003596:Cytosine; C011067:phosphoramidic acid