Leszczynska Grazyna, Sadowska Klaudia, Sierant Malgorzata, Sobczak Milena, Nawrot Barbara, Sochacka Elzbieta
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
Org Biomol Chem. 2017 Jun 27;15(25):5332-5336. doi: 10.1039/c7ob01012e.
S-Geranylated 2-thiouridines (geS2Us) are unique hydrophobic modified nucleosides identified very recently in bacterial tRNAs. Our study on the synthesis of geS2Ura-containing oligonucleotides (geS2U-RNA and geS2dU-DNA) revealed a fast substitution of the S-geranyl moiety by methylamine (frequently used in oligonucleotide deprotection procedures) or n-butylamine, providing the corresponding N2-alkyl isocytosine (R2isoCyt) derivatives. To retain the S-geranyl moiety in the DNA or RNA chains, the optimized deprotection protocol with 8 M ethanolic ammonia should be applied. The oligomers bearing the R2isoCyt heterocycle (R2isoC-RNA and R2isodC-DNA) are less hydrophobic than the corresponding S2U- and geS2U-modified oligomers, whereas, contrary to the previously reported data, geS2dU-DNA and geS2U-RNA exhibit significantly higher lipophilicity than the parent S2Ura-containing oligonucleotides. Thermodynamic studies revealed that: (a) both geS2Ura- and R2isoCyt-modified oligomers exhibit similar hybridization properties towards DNA and RNA templates, and (b) the R2isoCyt nucleobase preferentially hybridizes to guanine moiety in the DNA/DNA and RNA/RNA duplexes.
S-香叶基化2-硫代尿苷（geS2Us）是最近在细菌tRNA中发现的独特的疏水修饰核苷。我们对含geS2Ura的寡核苷酸（geS2U-RNA和geS2dU-DNA）合成的研究表明，甲胺（常用于寡核苷酸脱保护过程）或正丁胺会快速取代S-香叶基部分，生成相应的N2-烷基异胞嘧啶（R2isoCyt）衍生物。为了在DNA或RNA链中保留S-香叶基部分，应采用8 M乙醇氨的优化脱保护方案。带有R2isoCyt杂环的寡聚物（R2isoC-RNA和R2isodC-DNA）的疏水性低于相应的S2U-和geS2U-修饰的寡聚物，然而，与先前报道的数据相反，geS2dU-DNA和geS2U-RNA的亲脂性明显高于母体含S2Ura的寡核苷酸。热力学研究表明：（a）geS2Ura-和R2isoCyt-修饰的寡聚物对DNA和RNA模板表现出相似的杂交特性，并且（b）R2isoCyt核碱基在DNA/DNA和RNA/RNA双链体中优先与鸟嘌呤部分杂交。
