Parallel Stranded DNA Stabilized with Internal Sugar Cross-Links: Synthesis and Click Ligation of Oligonucleotides Containing 2′-Propargylated Isoguanosine

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 adeninethymine 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 (Delta T-m from +16 to +18.5 degrees C) with a similar increase as for aps DNA.