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

<p>&bdquo;Impact of a Single Nucleotide Change or Non-Nucleoside Modifications in G-Rich Region on the Quadruplex&ndash;Duplex Hybrid Formation&rdquo;.</p> <p>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&ndash;duplex hybrid (QDH) and duplex with dangling ends (Dss), after hybridization of RNA G-rich oligonucleotides with target sequences containing 5&prime;&ndash;GGGCUGG&ndash;3&prime; (U^T) or 5&prime;&ndash;GGGCGGG&ndash;3&prime; (G^T) 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.</p> <p><a href="https://www.mdpi.com/2218-273X/11/8/1236">https://www.mdpi.com/2218-273X/11/8/1236</a>, <a href="https://doi.org/10.3390/biom11081236">https://doi.org/10.3390/biom11081236</a></p> <p>Files are available in original formats: .xlsx, .opi, bruker, MultiGauge raw-image file (.img), JPG file (.jpg), text document (.txt)</p>