Improved performances of catalytic G-quadruplexes (G4-DNAzymes) via the chemical modifications of the DNA backbone to provide G-quadruplexes with double 3'-external G-quartets.

Fiche publication

Date publication

novembre 2019

Journal

International journal of biological macromolecules

Auteurs

Membres identifiés du Cancéropôle Est :
Dr MONCHAUD David

Tous les auteurs :
Virgilio A, Esposito V, Lejault P, Monchaud D, Galeone A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31747569

Résumé

Here we report on the design of a new catalytic G-quadruplex-DNA system (G4-DNAzyme) based on the modification of the DNA scaffold to provide the DNA pre-catalyst with two identical 3'-ends, known to be more catalytically proficient than the 5'-ends. To this end, we introduced a 5'-5' inversion of polarity sites in the middle of the G4-forming sequences AGA and AGA to obtain d(AGG-GGA) (or AG-GA) and d(AGGG-GGGA) (or AG-GA) that fold into stable G4 whose tetramolecular nature was confirmed via nuclear magnetic resonance (NMR) and circular dichroism (CD) investigations. Both AG-GA and AG-GA display two identical external G-quartets (3'-ends) known to interact with the cofactor hemin with a high efficiency, making the resulting complex competent to perform hemoprotein-like catalysis (G4-DNAzyme). A systematic comparison of the performances of modified and unmodified G4s lends credence to the relevance of the modification exploited here (5'-5' inversion of polarity site), which represents a new chemical opportunity to improve the overall activity of catalytic G4s.