Improvement of a streptavidin-binding aptamer by LNA- and α-l-LNA-substitutions

Probing the Key Binding Sequence and Improvement of the Stability of a β‐Bungarotoxin‐binding Aptamer in Snake Venom

“…LNAs, which are sugar modified nucleic acid analogues containing a methylene linkage between the 2 0 oxygen and the 4 0 carbon of the ribose ring (Figure 2), display unprecedented hybridization affinity toward complementary DNA (or RNA), enhanced duplex thermal stability, and increased resistance to degradation by nucleases. [29][30][31] As the S2 duplex did not directly participate in binding but was essential for the stabilization of the overall aptamer structure, we introduced LNA modifications in S2, aiming at improving stem stabilization and nuclease resistance while maintaining its binding affinity to the target. When the two distal base pairs of the aptamer βB-1.11 were replaced by LNAs (βB-1.11L1, Table S2), the Δr reached 0.0214 in competitive displacement assay whereas that of βB-1.11 was 0.0195 ( Figure S2), which indicated that the binding affinity of βB-1.11L1 was increased compared with that of βB-1.11.…”

“…LNAs, which are sugar modified nucleic acid analogues containing a methylene linkage between the 2′ oxygen and the 4′ carbon of the ribose ring (Figure ), display unprecedented hybridization affinity toward complementary DNA (or RNA), enhanced duplex thermal stability, and increased resistance to degradation by nucleases . As the S2 duplex did not directly participate in binding but was essential for the stabilization of the overall aptamer structure, we introduced LNA modifications in S2, aiming at improving stem stabilization and nuclease resistance while maintaining its binding affinity to the target.…”

Towards applications of synthetic genetic polymers in diagnosis and therapy

“…However, full substitution may not always be necessary to achieve stabilisation: Shi et al (2014) have shown how a DNA aptamer selected to bind lymphoma Ramos cells need not be completely modified with locked nucleic acid (LNA) and a 3 0 3 0 -thymidine cap in order to achieve an approximately ten-fold enhancement in serum stability [7]. Likewise, Jørgensen et al [8] have shown that even partial LNA and a-L-LNA modification of anti-streptavidin DNA aptamers can improve both binding and nuclease resistance.…”

Chemical Modification of Aptamers for Increased Binding Affinity in Diagnostic Applications: Current Status and Future Prospects

“…Depending on the position, LNA aptamers showed a decreased or comparable biological affinity compared to the unmodified aptamer. Since this report, multiple aptamers such as the (strept)avidin binding aptamer [ 152 , 153 ], the Sgc8 aptamer [ 154 ] and the TD05 aptamer [ 155 ] have been modified with LNA, with a similar result in all cases. In general, the structural changes and biological effects that LNA modifications impose are dependent on the position and number of modifications.…”