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Locked nucleic acid building blocks as versatile tools for advanced G-quadruplex design.

ABSTRACT: A hybrid-type G-quadruplex is modified with LNA (locked nucleic acid) and 2'-F-riboguanosine in various combinations at the two syn positions of its third antiparallel G-tract. LNA substitution in the central tetrad causes a complete rearrangement to either a V-loop or antiparallel structure, depending on further modifications at the 5'-neighboring site. In the two distinct structural contexts, LNA-induced stabilization is most effective compared to modifications with other G surrogates, highlighting a potential use of LNA residues for designing not only parallel but various more complex G4 structures. For instance, the conventional V-loop is a structural element strongly favored by an LNA modification at the V-loop 3'-end in contrast with an alternative V-loop, clearly distinguishable by altered conformational properties and base-backbone interactions as shown in a detailed analysis of V-loop structures.

SUBMITTER: Haase L

PROVIDER: S-EPMC7544228 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Locked nucleic acid building blocks as versatile tools for advanced G-quadruplex design.

Haase Linn L Weisz Klaus K

Nucleic acids research 20201001 18

A hybrid-type G-quadruplex is modified with LNA (locked nucleic acid) and 2'-F-riboguanosine in various combinations at the two syn positions of its third antiparallel G-tract. LNA substitution in the central tetrad causes a complete rearrangement to either a V-loop or antiparallel structure, depending on further modifications at the 5'-neighboring site. In the two distinct structural contexts, LNA-induced stabilization is most effective compared to modifications with other G surrogates, highlig ...[more]

PMID: 32890406

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