Laboratory of Biomedical Chemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, 630090, Russia; Novosibirsk State University, Novosibirsk, 630090, Russia.
Laboratory of Biomedical Chemistry, Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, 630090, Russia; Novosibirsk State University, Novosibirsk, 630090, Russia.
Biochem Biophys Res Commun. 2021 Nov 5;577:110-115. doi: 10.1016/j.bbrc.2021.09.001. Epub 2021 Sep 4.
Phosphoryl guanidine oligonucleotides (PGOs) are promising uncharged analogs of nucleic acids and are used in a variety of applications. The importance of hydration is frequently ignored during the design of modified nucleic acid probes. Such hydrophobic modifications (phosphoryl guanidine) are expected to have a significant impact on the structure and thermal stability of the affected oligo with complementary nucleic acids. Here we aimed to investigate (by the osmotic stress method) hydration changes upon the formation of a duplex of a PGO with complementary DNA. According to our results, the presence of phosphoryl guanidines in one or both strands of a duplex only minimally affects hydration alterations under crowding conditions. The secondary structure of native and modified duplexes did not change significantly in the presence of ethanol, ethylene glycol, polyethylene glycol 200, or polyethylene glycol 1000. After the addition of a cosolvent, the thermodynamic stability of the PGO complexes changed in the same manner as that seen in a corresponding DNA duplex. The findings reported here and our previous studies form the basis for efficient use of PGOs in basic research and a variety of applications.
磷酸胍寡核苷酸 (PGO) 是一种有前途的非带电核酸类似物，在各种应用中都有使用。在设计修饰核酸探针时，通常会忽略水合作用的重要性。这种疏水性修饰（磷酸胍）预计会对受影响的寡核苷酸与互补核酸的结构和热稳定性产生重大影响。在这里，我们旨在通过渗透压力法研究形成 PGO 与互补 DNA 双链体时的水合变化。根据我们的结果，在拥挤条件下，双链体中一条或两条链上存在磷酸胍仅最小限度地影响水合变化。在存在乙醇、乙二醇、聚乙二醇 200 或聚乙二醇 1000 的情况下，天然和修饰的双链体的二级结构没有发生显著变化。加入共溶剂后，PGO 配合物的热力学稳定性以与相应 DNA 双链体相同的方式发生变化。这里报告的发现和我们之前的研究为在基础研究和各种应用中有效使用 PGO 奠定了基础。
