Synthèse et étude d'oligonucléotides circularisables sur des cibles ADN et ARN (utilisation de chélateurs de métaux)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Targeting of single stranded oligonucleotides through metal-induced cyclization of short complementary strands: Targeting of single stranded oligonucleotides

International audienceA new strategy to cyclize a short synthetic oligonucleotide on a DNA or a RNA target strand is described. This one relies on a metal-mediated cyclization of short synthetic oligonucleotides conjugated with two chelating 2,2':6',2”-terpyridine moieties at their 3' and 5' ends. Cyclization following metal addition (Zn2+, Fe2+) was demonstrated using UV monitored thermal denaturation experiments, mass spectrometry analysis and gel shift assays. NMR experiments were used to analyse the association of complementary strands after metal-mediated cyclization. We have thus demonstrated that an efficient circularization of synthetic oligonucleotides is easily achieved through this strategy. The hybridization on a complementary strand was more efficient with a RNA target strand and a 2'-O-methyl circularized oligomer