Features of "All LNA" Duplexes Showing a New Type of Nucleic Acid Geometry.
"Locked nucleic acids" (LNAs) belong to the backbone-modified nucleic acid family. The 2'-O,4'-C-methylene-β-D-ribofuranose nucleotides are used for single or multiple substitutions in RNA molecules and thereby introduce enhanced bio- and thermostability. This renders LNAs powerful tools for diagnostic and therapeutic applications. RNA molecules maintain the overall canonical A-type conformation upon substitution of single or multiple residues/nucleotides by LNA monomers. The structures of "all" LNA homoduplexes, however, exhibit significant differences in their overall geometry, in particular a decreased twist, roll and propeller twist. This results in a widening of the major groove, a decrease in helical winding, and an enlarged helical pitch. Therefore, the LNA duplex structure can no longer be described as a canonical A-type RNA geometry but can rather be brought into proximity to other backbone-modified nucleic acids, like glycol nucleic acids or peptide nucleic acids. LNA-modified nucleic acids provide thus structural and functional features that may be successfully exploited for future application in biotechnology and drug discovery.
Institut für Chemie und Biochemie, Freie Universität Berlin, 14195 Berlin, Germany.
Charlotte
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Förster
André
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Eichert
Dominik
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Oberthür
Christian
C
Betzel
Reinhard
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Geßner
Andreas
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Nitsche
Jens P
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