The Synthesis of 2′-O-Methyl G-Clamp Containing Oligonucleotides and Their Inhibition of the HIV-1 Tat-TAR Interaction

Abstract

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.