Pils W, Micura R
Institut für Chemie, Johannes Kepler Universität, Altenbergerstrasse 69, A-4040 Linz, Austria.
Nucleic Acids Res. 2000 May 1;28(9):1859-63. doi: 10.1093/nar/28.9.1859.
Ethylene glycol oligomers have been studied systematically as non-nucleotide loop replacements in short hairpin oligoribonucleotides. Structural optimization concerns the length of the linkers and is based on the thermodynamic stabilities of the corresponding duplexes. The optimum linker is derived from heptakis (ethylene glycol) provided that the duplex end to be bridged comprises solely the terminal base pair; the optimum linker is derived from hexakis(ethylene glycol) if a dangling unpaired nucleotide is incorporated into the loop. Moreover, these linkers have been compared to other commonly used linker types which consist of repeating units of tris- or tetrakis(ethylene glycol) phosphate, or of 3-hydroxypropane-1-phosphate. In all cases, the correlation between linker length and duplex stability is independent of the kind of counter ions used (Na(+), Na(+)/Mg(2+), K(+)or Li(+)). Furthermore, all duplexes with non-nucleotide loop replacements are less stable than those with the corresponding standard nucleotide loop. The results corroborate that the linkers are solvent-exposed and do not specifically interfere with the terminal nucleotides at the bridged duplex end.
乙二醇低聚物已被系统地研究作为短发夹寡核糖核苷酸中的非核苷酸环替代物。结构优化涉及连接子的长度，并基于相应双链体的热力学稳定性。如果要桥接的双链体末端仅包含末端碱基对，则最佳连接子衍生自七聚乙二醇；如果环中掺入了一个悬垂的未配对核苷酸，则最佳连接子衍生自六聚乙二醇。此外，还将这些连接子与其他常用的连接子类型进行了比较，后者由磷酸三或四聚乙二醇的重复单元或3-羟基丙烷-1-磷酸组成。在所有情况下，连接子长度与双链体稳定性之间的相关性与所使用的抗衡离子种类（Na⁺、Na⁺/Mg²⁺、K⁺或Li⁺）无关。此外，所有具有非核苷酸环替代物的双链体都比具有相应标准核苷酸环的双链体稳定性低。结果证实连接子暴露于溶剂中，并且不会特异性干扰桥接双链体末端的末端核苷酸。
