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 |
Zur Langanzeige
Seitenaufrufe
6
Letzte Woche
0
0
Letzter Monat
0
0
geprüft am 21.05.2024