Teplova M, Minasov G, Tereshko V, Inamati G B, Cook P D, Manoharan M, Egli M
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Nat Struct Biol. 1999 Jun;6(6):535-9. doi: 10.1038/9304.
2'-O-(2-Methoxyethyl)-RNA (MOE-RNA) is a nucleic acid analog with promising features for antisense applications. Compared with phosphorothioate DNA (PS-DNA), the MOE modification offers improved nuclease resistance, enhanced RNA affinity, improved cellular uptake and intestinal absorption, reduced toxicity and immune stimulation. The crystal structure of a fully modified MOE-RNA dodecamer duplex (CGCGAAUUCGCG) was determined at 1.7 A resolution. In the majority of the MOE substituents, the torsion angle around the ethylene alkyl chain assumes a gauche conformation. The conformational preorganization of the MOE groups is consistent with the improved RNA affinity and the extensive hydration of the substituents could play a role in the improved cellular uptake of MOE-RNA. A specific hydration pattern that bridges substituent and phosphate oxygen atoms in the minor groove of MOE-RNA may explain its high nuclease resistance.
2'-O-(2-甲氧基乙基)-RNA（MOE-RNA）是一种核酸类似物，在反义应用方面具有良好特性。与硫代磷酸酯DNA（PS-DNA）相比，MOE修饰具有更高的核酸酶抗性、更强的RNA亲和力、更好的细胞摄取和肠道吸收能力、更低的毒性以及免疫刺激作用。一个完全修饰的MOE-RNA十二聚体双链体（CGCGAAUUCGCG）的晶体结构在1.7埃分辨率下得以确定。在大多数MOE取代基中，围绕亚乙基烷基链的扭转角呈现gauche构象。MOE基团的构象预组织与增强的RNA亲和力相一致，并且取代基的广泛水合作用可能在MOE-RNA改善的细胞摄取中发挥作用。一种在MOE-RNA小沟中连接取代基和磷酸氧原子的特定水合模式可能解释了其高核酸酶抗性。
