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
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 site in the middle of the G4-forming sequences AG 4 A and AG 6 A to obtain d(3' AGG 5'-5' GGA 3') (or AG 2-G 2 A) and d(3' AGGG 5'-5' GGGA 3') (or AG 3-G 3 A) that fold into stable G4 whose tetramolecular nature was confirmed via nuclear magnetic resonance (NMR) and circular dichroism (CD) investigations. Both AG 2-G 2 A and AG 3-G 3 A 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.
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