Surprising duplex stabilisation upon mismatch introduction within triply modified duplexes

Three different modified phosphoramidite nucleoside building blocks equipped with additional protected imidazole, masked alcohol and masked carboxylate functionality are synthesized and incorporated into oligonucleotides. Based on the serine-protease active site model, doubly and triply modified duplexes are created and tested for stability. Analysis of different spatial distributions of the extra functionalities shows that careful positioning can even overcome duplex destabilisation caused by the introduction of mismatches.

Based on the serine-protease active site model, doubly and triply modified duplexes have been synthesized and tested for stability, considering different spatial distributions of functionalities.Figure optionsDownload as PowerPoint slide