Title
2’-O-Methyl- and 2’-O-propargyl-5-methylisocytidine: synthesis, properties and impact on the isoCd – dG and the isoCd – isoGd base pairing in nucleic acids with parallel and antiparallel strand orientation
Author
Sunit Kumar Jana, Peter Leonard, Sachin A. Ingale, Frank Seela
Year
2016
Journal
Organic and Biomolecular Chemistry
Abstract
Oligonucleotides containing 2′-O-methylated 5-methylisocytidine (3) and 2′-O-propargyl-5-methylisocytidine (4) as well as the non-functionalized 5-methyl-2′-deoxyisocytidine (1b) were synthesized. MALDI-TOF mass spectra of oligonucleotides containing 1b are susceptible to a stepwise depyrimidination. In contrast, oligonucleotides incorporating 2′-O-alkylated nucleosides 3 and 4 are stable. This is supported by acid catalyzed hydrolysis experiments performed on nucleosides in solution. 2′-O-Alkylated nucleoside 3 was synthesized from 2′-O-5-dimethyluridine via tosylation, anhydro nucleoside formation and ring opening. The corresponding 4 was obtained by direct regioselective alkylation of 5-methylisocytidine (1d) with propargyl bromide under phase-transfer conditions. Both compounds were converted to phosphoramidites and employed in solid-phase oligonucleotide synthesis. Hybridization experiments resulted in duplexes with antiparallel or parallel chains. In parallel duplexes, methylation or propargylation of the 2′-hydroxyl group of isocytidine leads to destabilization while in antiparallel DNA this effect is less pronounced. 2′-O-Propargylated 4 was used to cross-link nucleosides and oligonucleotides to homodimers by a stepwise click ligation with a bifunctional azide.
Instrument
J-815
Keywords
Circular dichroism, DNA structure, Ligand binding, Biochemistry