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. Issue 21 (12th May 2016)

• Record Type: Journal Article
• Authors: Jana, Sunit K.; Leonard, Peter; Ingale, Sachin A.; Seela, Frank
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 21(2016)
• Page Start: 4927
• Page End: 4942
• Publication Date: 2016-05-12
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c6ob00622a
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : The impact of 2′- O -alkyl residues on the stability of iCd –dG and iCd –iGd base pairs was studied in DNA with parallel and antiparallel chain 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 containing1b are susceptible to a stepwise depyrimidination. In contrast, oligonucleotides incorporating 2′- O -alkylated nucleosides3 and4 are stable. This is supported by acid catalyzed hydrolysis experiments performed on nucleosides in solution. 2′- O -Alkylated nucleoside3 was synthesized from 2′- O -5-dimethyluridine via tosylation, anhydro nucleoside formation and ring opening. The corresponding4 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 -Propargylated4 was used to cross-link nucleosides and oligonucleotides to homodimers by a stepwise click ligation with a bifunctional azide.