Reaction of S-geranyl-2-thiouracil modified oligonucleotides with alkyl amines leads to the N2-alkyl isocytosine derivatives. Issue 25 (15th June 2017)

• Record Type: Journal Article
• Authors: Leszczynska, Grazyna; Sadowska, Klaudia; Sierant, Malgorzata; Sobczak, Milena; Nawrot, Barbara; Sochacka, Elzbieta
• Is Part Of: Organic & biomolecular chemistry. Volume 15:Issue 25(2017)
• Page Start: 5332
• Page End: 5336
• Publication Date: 2017-06-15
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob01012e
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : The yield of the synthesis of S -geranylated oligomers depends on the alkaline conditions of oligomer deprotection; a routinely used alkyl amine protocol delivers N 2-alkyl iso cytosine-modified side products. Abstract : 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 N 2-alkyl iso cytosine (R2 iso Cyt) 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 R2 iso Cyt heterocycle (R2 iso C-RNA and R2 iso dC-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 R2 iso Cyt-modified oligomers exhibit similar hybridization properties towards DNA and RNA templates, and (b) the R2 iso Cyt nucleobase preferentially hybridizes to guanine moiety in the DNA/DNA and RNA/RNA duplexes.