The Journal of organic chemistry

Parallel stranded DNA stabilized with internal sugar cross-links: synthesis and click ligation of oligonucleotides containing 2'-propargylated isoguanosine.

PMID 23915305


Internal sugar cross-links were introduced for the first time into oligonucleotides with parallel chain orientation by click ligation. For this, the 2'- or 3'-position of the isoguanosine ribose moiety was functionalized with clickable propargyl residues, and the synthesis of propargylated cytosine building blocks was significantly improved. Phosphoramidites were prepared and employed in solid-phase synthesis. A series of oligo-2'-deoxyribonucleotides with parallel (ps) and antiparallel (aps) strand orientation were constructed containing isoguanine-cytosine, isoguanine-isocytosine, and adenine-thymine base pairs. Complementary oligonucleotides with propargylated sugar residues were ligated in a stepwise manner with a chelating bis-azide under copper catalysis. Cross-links were introduced within a base pair or in positions separated by two base pairs. From T(m) stability studies it is evident that cross-linking stabilizes DNA with parallel strand orientation strongly (ΔT(m) from +16 to +18.5 °C) with a similar increase as for aps DNA.