Institute of Organic Chemistry and Biochemistry AS CR, v.v.i., Flemingovo nam. 2, 16610, Prague, Czech Republic.
Org Biomol Chem. 2011 Sep 7;9(17):6120-6. doi: 10.1039/c1ob05488k. Epub 2011 Jul 18.
Solid phase synthesis of phosphonate-modified oligoribonucleotides using 2'-O-benzoyloxymethoxymethyl protected monomers is presented in both 3'→5' and 5'→3' directions. Hybridisation properties and enzymatic stability of oligoribonucleotides modified by regioisomeric 3'- and 5'-phosphonate linkages are evaluated. The introduction of the 5'-phosphonate units resulted in moderate destabilisation of the RNA/RNA duplexes (ΔT(m)-1.8 °C/mod.), whereas the introduction of the 3'-phosphonate units resulted in considerable destabilisation of the duplexes (ΔT(m)-5.7 °C/mod.). Molecular dynamics simulations have been used to explain this behaviour. Both types of phosphonate linkages exhibited remarkable resistance in the presence of ribonuclease A, phosphodiesterase I and phosphodiesterase II.
采用 2'-O-苯甲酰氧甲基甲氧甲基保护单体，在 3'→5'和 5'→3'方向上进行了膦酸酯修饰寡核糖核苷酸的固相合成。评估了通过区域异构体 3'-和 5'-膦酸酯键修饰的寡核糖核苷酸的杂交性质和酶稳定性。引入 5'-膦酸酯单元导致 RNA/RNA 双链体适度失稳（ΔT(m)-1.8°C/mod.），而引入 3'-膦酸酯单元则导致双链体显著失稳（ΔT(m)-5.7°C/mod.）。分子动力学模拟被用来解释这种行为。这两种膦酸酯键在核糖核酸酶 A、磷酸二酯酶 I 和磷酸二酯酶 II 的存在下均表现出显著的抗性。
