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.
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.
authors.affiliation: Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany. Frank.Seela@uni-osnabrueck.de.
authors.forename: Sunit K
authors.initials: SK
authors.lastname: Jana
authors.forename: Peter
authors.initials: P
authors.lastname: Leonard
authors.forename: Sachin A
authors.initials: SA
authors.lastname: Ingale
authors.forename: Frank
authors.initials: F
authors.lastname: Seela
mesh_terms: D020029:Base Pairing; D060326:Chemistry Techniques, Synthetic; D003562:Cytidine / Q000138:chemical synthesis* / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000737:chemistry*
chemical_list: C083576:isocytidine; D003562:Cytidine; D012313:RNA; D004247:DNA