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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.

SUBMITTER: Sczepanski JT

PROVIDER: S-EPMC3804424 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Binding of a structured D-RNA molecule by an L-RNA aptamer.

Sczepanski Jonathan T JT Joyce Gerald F GF

Journal of the American Chemical Society 20130828 36

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 ...[more]

PMID: 23977945

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