Moody H M, van Genderen M H, Koole L H, Kocken H J, Meijer E M, Buck H M
Department of Organic Chemistry, Eindhoven University of Technology, The Netherlands.
Nucleic Acids Res. 1989 Jun 26;17(12):4769-82. doi: 10.1093/nar/17.12.4769.
A new synthesis route for long phosphate-methylated oligodeoxynucleotides is described, which were used as antisense inhibitors of the DNA replication. Phosphate-methylated oligomers hybridize more strongly with natural DNA than their natural analogues, due to the absence of electrostatic interstrand repulsions. Compared with phosphate-ethylated and methyl phosphonate systems, phosphate-methylated systems are preferable as antisense DNA, which was concluded from the high Tm values and sharp melting transitions of duplexes of phosphate-methylated and natural DNA. By using the Sanger dideoxy technique, it was shown that a complementary phosphate-methylated 18-mer can effectively and site-specifically block the DNA replication process at room temperature.
描述了一种用于长磷酸甲基化寡脱氧核苷酸的新合成路线，其用作DNA复制的反义抑制剂。由于不存在静电链间排斥，磷酸甲基化寡聚物与其天然类似物相比，与天然DNA的杂交更强。与磷酸乙基化和甲基膦酸酯体系相比，磷酸甲基化体系作为反义DNA更具优势，这是从磷酸甲基化与天然DNA双链体的高熔点值和尖锐的解链转变得出的结论。通过使用桑格双脱氧技术表明，互补的磷酸甲基化18聚体在室温下可以有效且位点特异性地阻断DNA复制过程。
