title: Binding of a structured D-RNA molecule by an L-RNA aptamer.
abstract: An L-RNA aptamer was developed that binds the natural D-form of the HIV-1 trans-activation responsive (TAR) RNA. The aptamer initially was obtained as a D-aptamer against L-TAR RNA through in vitro selection. Then the corresponding L-aptamer was prepared by chemical synthesis and used to bind the desired target. The L-aptamer binds D-TAR RNA with a Kd of 100 nM. It binds D-TAR exclusively at the six-nucleotide distal loop, but does so through tertiary interactions rather than simple Watson-Crick pairing. This complex is the first example of two nucleic acids molecules of opposing chirality that interact through a mode of binding other than primary structure. Binding of the L-aptamer to D-TAR RNA inhibits formation of the Tat-TAR ribonucleoprotein complex that is essential for TAR function. This suggests that L-aptamers, which are intrinsically resistant to degradation by ribonucleases, might be pursued as an alternative to antisense oligonucleotides to target structured RNAs of biological or therapeutic interest.
authors: Departments of Chemistry and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors: Jonathan T
authors: JT
authors: Sczepanski
authors: Gerald F
authors: GF
authors: Joyce
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001665:Binding Sites; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*
chemical_list: D052157:Aptamers, Nucleotide; C002612:DNA-like RNA; D012313:RNA
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