1451256-05-5Relevant academic research and scientific papers
Oligonucleotides with clickable sugar residues: Synthesis, duplex stability, and terminal versus central interstrand cross-linking of 2′-O-propargylated 2-aminoadenosine with a bifunctional azide
Pujari, Suresh S.,Leonard, Peter,Seela, Frank
, p. 4423 - 4437 (2014)
Duplex DNA with terminal and internal sugar cross-links were synthesized by the CuAAC reaction from oligonucleotides containing 2′-O-propargyl-2- aminoadenosine as a clickable site and a bifunctional azide (4). Stepwise click chemistry was employed to introduce cross-links at internal and terminal positions. Copper turnings were used as catalyst, reducing the copper load of the reaction mixture and avoiding complexing agents. For oligonucleotide building block synthesis, a protecting group strategy was developed for 2′-O-propargyl-2-aminoadenosine owing to the rather different reactivities of the two amino groups. Phosphoramidites were synthesized bearing clickable 2′-O-propargyl residues (14 and 18) as well as a 2′- deoxyribofuranosyl residue (10). Hybridization experiments of non-cross-linked oligonucleotides with 2,6-diaminopurine as nucleobase showed no significant thermal stability changes over those containing adenine. Surprisingly, an isobutyryl group protecting the 2-amino function has no negative impact on the stability of DNA-DNA and DNA-RNA duplexes. Oligonucleotide duplexes with cross-linked 2′-O-propargylated 2-aminoadenosine (1) and 2′-O-propargylated adenosine (3) at terminal positions are significantly stabilized (ΔTm = +29 °C). The stability results from a molecularity change from duplex to hairpin melting and is influenced by the ligation position. Terminal ligation led to higher melting duplexes than corresponding hairpins, while duplexes with central ligation sites were less stable.
Parallel stranded DNA stabilized with internal sugar cross-links: Synthesis and click ligation of oligonucleotides containing 2′-propargylated isoguanosine
Pujari, Suresh S.,Seela, Frank
, p. 8545 - 8561 (2013/09/24)
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 Tm stability studies it is evident that cross-linking stabilizes DNA with parallel strand orientation strongly (ΔTm from +16 to +18.5 C) with a similar increase as for aps DNA.
