The Eight Stereoisomers of LNA (Locked Nucleic Acid): A Remarkable Family of Strong RNA Binding Molecules

Flexible and Frozen Sugar-Modified Nucleic Acids - Modulation of Biological Activity Through Furanose Ring Dynamics in the Antisense Strand

“…Likewise, the locked nucleic acids (LNA) and related chemical variants [109][110][111][112], which possess a [2.2.1]bicyclic ribosyl-configured frame (Fig. 6c), have taken advantage of conformational restriction to induce unparalleled increases in the thermal stability of duplexes toward complementary DNA and RNA (∆T M /monomer = 3 -11 o C vs. a DNA reference) [113,114].…”

α-LNA (Locked Nucleic Acid withα-D-Configuration): Synthesis and Selective Parallel Recognition of RNA

“…Thus, the stereoisomers of LNA, including the enantiomer of a-LNA, that is a-l-LNA, [18] have recently been demonstrated to be a class of very efficient RNAbinding nucleic acid analogues. [19] Recently, in a preliminary form, we introduced the synthesis and hybridisation properties of a-LNA containing only the thymine monomer 2. [20,21] Thus, a fully modified a-LNA sequence (aT L 10 was found to form a very stable duplex with complementary RNA (rA 14 ).…”

“…The increase in thermal stability found was 1.2 8C per modification relative to the corresponding a-DNA sequence (aT 10 ) and 2.5 8C per modification relative to T 10 ( Table 1). [20] Thus, a-LNA was found to display an affinity towards RNA comparable to that of other stereoisomers of LNA, [19] and although not quite as high as that of the original LNA, [15,19] this is unprecedented among a-d-configured nucleic acid analogues. However, these preliminary results could neither answer the question as to whether a-LNA prefers parallel or antiparallel strand orientation, nor explain the apparently strong selectivity for hybridisation with complementary RNA over DNA.…”

Locked nucleic acid: tighter is different

“…26 Finally it should be noted that the full family of eight LNArelated stereoisomers has been tested and remarkably, six of them bind RNA with high affinity. 27 Among these, α-L-LNA shows 5 considerable promise (Figure 3d). In contrast to LNA, which induces strongly A-form helices, α-L-LNA leads to a more Bform helical structure.…”