Guan Z, Jin H W, Yang Z J, Zhang L R, Zhang L H
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Drug Discov Ther. 2007 Aug;1(1):65-72.
Oligonucleotides consisting of isonucleoside 2',5'-anhydro-3'-nucleobase-D-mannitol incorporated in 1'→4' linkage mode were synthesized. Their binding behaviors with complementary sequences were investigated via thermal denaturation and CD spectra. 6' O-methyl-2',5'-anhydro-3'-(thymin-1-yl)-D-mannitol incorporated oligonucleotide was also synthesized to investigate the effect of hydroxy groups of isonucleosides on duplex formation. The results showed that the 6'-OH free isonucleosidemodified oligonucleotide was able to form a B-like duplex with 3'→5' complementary native oligodeoxynucleotide in the 1'→4' direction. The free hydroxy group in the isonucleoside made a significant contribution to the affinity of the modified oligonucleotide to the complementary sequence, which was confirmed by molecular dynamics simulation.
合成了由以1'→4'连接模式掺入的异核苷2',5'-脱水-3'-核苷碱基-D-甘露糖醇组成的寡核苷酸。通过热变性和圆二色光谱研究了它们与互补序列的结合行为。还合成了掺入6'-O-甲基-2',5'-脱水-3'-(胸腺嘧啶-1-基)-D-甘露糖醇的寡核苷酸，以研究异核苷羟基对双链体形成的影响。结果表明，6'-OH游离的异核苷修饰寡核苷酸能够在1'→4'方向上与3'→5'互补天然寡脱氧核苷酸形成类B双链体。分子动力学模拟证实，异核苷中的游离羟基对修饰寡核苷酸与互补序列的亲和力有显著贡献。
