Application of Cu(I)-catalyzed azide-alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

Svetlana V Vasilyeva; Vyacheslav V Filichev; Alexandre S Boutorine

doi:10.3762/bjoc.12.128

Application of Cu(I)-catalyzed azide-alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

Beilstein J Org Chem. 2016 Jun 30:12:1348-60. doi: 10.3762/bjoc.12.128. eCollection 2016.

Authors

Svetlana V Vasilyeva¹, Vyacheslav V Filichev², Alexandre S Boutorine³

Affiliations

¹ Institute of Chemical Biology & Fundamental Medicine, SB of RAS, pr. Lavrent'eva 8, 630090 Novosibirsk, Russia.
² Institute of Fundamental Sciences, Massey University, Private Bag 11-222, 4442 Palmerston North, New Zealand.
³ Structure and Instability of Genomes, Sorbonne Universités, Muséum National d'Histoire Naturelle, INSERM U 1154, CNRS UMR 7196, 57 rue Cuvier, C.P. 26, 75231 Paris cedex 05, France.

Abstract

Efficient protocols based on Cu(I)-catalyzed azide-alkyne cycloaddition were developed for the synthesis of conjugates of pyrrole-imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple helices by TFO-MGB conjugates was evaluated by gel-shift experiments. The presence of MGB in these conjugates did not affect the binding parameters (affinity and triplex stability) of the parent TFOs.

Keywords: Cu(I)-catalyzed azide–alkyne cycloaddition; binding affinity; click chemistry; pyrrole–imidazole polyamides; sequence specificity: DNA; triplex-forming oligonucleotides.