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  • Title: Hexitol nucleic acid-containing aptamers are efficient ligands of HIV-1 TAR RNA.
    Author: Kolb G, Reigadas S, Boiziau C, van Aerschot A, Arzumanov A, Gait MJ, Herdewijn P, Toulmé JJ.
    Journal: Biochemistry; 2005 Mar 01; 44(8):2926-33. PubMed ID: 15723535.
    Abstract:
    The transactivation responsive element (TAR) plays a crucial role in the transcription of the HIV-1 genome upon specific binding of the viral protein Tat and cellular proteins. We have previously identified a RNA hairpin aptamer forming a stable and specific kissing complex with TAR RNA (Ducongé, F., and Toulmé, J. J. (1999) RNA 5, 1605-1614). We chemically modified this aptamer with hexitol nucleic acid (HNA) residues. We demonstrate that a fully HNA-modified aptamer is a poor ligand but, in contrast, mixmers containing both HNA and unmodified RNA nucleotides display interesting properties. Two HNA-RNA mixmers bind to TAR with an equilibrium dissociation constant in the low-nanomolar range and show a reduced nuclease sensitivity. In addition, they show a moderate dependence on magnesium ions for binding to TAR. These HNA-RNA mixmers are able to inhibit transactivation of transcription in an in vitro assay.
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