Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation

„Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex–Duplex Hybrid Formation”.

In article, a method to discriminate between two target RNA sequences that differ by one nucleotide only is presented. The method relies on the formation of alternative structures, i.e., quadruplex–duplex hybrid (QDH) and duplex with dangling ends (Dss), after hybridization of RNA G-rich oligonucleotides with target sequences containing 5′–GGGCUGG–3′ (UT) or 5′–GGGCGGG–3′ (GT) fragments. Using biophysical methods, the effect of covalently attached G4 ligand on the ability of G-rich oligonucleotides to assemble a G-quadruplex motif was studied. The sequence-guided o-BMVC G4-ligand acted as a quadruplex stabilizer but not duplex. The use of such conjugates (o-BMVC-RNA) creates the possibility of inducing and stabilizing the bimolecular quadruplexes on the G-rich mRNA template in a sequence-specific manner. The formation of QDH or Dss structures is dependent on a single nucleotide change in the target sequence, and the possibility to selectively stabilize the G-quadruplex domain by attaching the G4 ligand may become an attractive alternative therapy for patients with an EGFR-L858R mutation.

https://www.mdpi.com/2218-273X/11/8/1236, https://doi.org/10.3390/biom11081236

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