2 `-O-Methyl- and 2 `-O-propargyl-5-methylisocytidine: synthesis, properties and impact on the isoC(d)-dG and the isoC(d)-isoG(d) base pairing in nucleic acids with parallel and antiparallel strand orientation

Autor(en): Jana, Sunit K.
Leonard, Peter
Ingale, Sachin A.
Seela, Frank
Stichwörter: CATALYZED HYDROLYSIS; CHAIN ORIENTATION; Chemistry; Chemistry, Organic; CLICK CHEMISTRY; DNA DUPLEX; DOUBLE HELIX; ENZYMATIC INCORPORATION; MASS-SPECTROMETRY; OLIGONUCLEOTIDE DUPLEXES; RESIDUES SYNTHESIS; TERMINAL ALKYNES
Erscheinungsdatum: 2016
Herausgeber: ROYAL SOC CHEMISTRY
Journal: ORGANIC & BIOMOLECULAR CHEMISTRY
Volumen: 14
Ausgabe: 21
Startseite: 4927
Seitenende: 4942
Zusammenfassung: 
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.
ISSN: 14770520
DOI: 10.1039/c6ob00622a

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