Biomolecular Nanoscale Engineering Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark , Campusvej 55, 5230 Odense M, Denmark.
Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas, CSIC Universidad de Sevilla , Americo Vespucio 49, 41092 Sevilla, Spain.
J Org Chem. 2016 Nov 18;81(22):10845-10856. doi: 10.1021/acs.joc.6b01917. Epub 2016 Oct 25.
Galactose-modified thymidine, LNA-T, and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'-functionalized 2'-amino-LNA derivatives in particular, showed improved duplex thermal stability against DNA and RNA complements and increased ability to discriminate mismatches. In addition, the 2'-amino-LNA-T derivatives induced remarkable 3'-exonuclease resistance. These results were further investigated using molecular modeling studies.
半乳糖修饰的胸苷、LNA-T 和 2'-氨基-LNA-T 核苷被合成，并转化为相应的磷酰胺衍生物，然后引入短寡核苷酸中。与未修饰的对照链相比，半乳糖修饰的寡核苷酸通常，特别是 N2'-功能化的 2'-氨基-LNA 衍生物，表现出与 DNA 和 RNA 互补物的热稳定性提高，并增加了区分错配的能力。此外，2'-氨基-LNA-T 衍生物诱导了显著的 3'-核酸外切酶抗性。这些结果通过分子建模研究进一步进行了研究。
