Fig 1.
Schematic representation of coaxial (left) and orthogonal (right) orientations present in typical Q–D junctions.
G-quadruplex sequences are reported in green, duplex sequences are in blue.
Fig 2.
Molecular structures of BMH-21, ST-1968 and DOXO.
Fig 3.
Schematic representation of a hybrid quadruplex-duplex conformation with a three-layered G-tetrad core arranged in a (3+1) topology and a long 12-nt loop forming a hairpin structure.
Fig 4.
Interaction of BMH-21 with the LTR-III structure.
A: The BMH-21/LTR-III complex was obtained by molecular docking and optimized by YASARA Structure [36], and it is represented as side (left) and top (right) views of the ghostly-white solvent-accessible surface (SAS) of the LTR-III target. The ligand was represented as van der Waals (vdW) spheres. The nucleotides are rendered in slabs and filled sugars (left) and mufflers and sugar as tubes (right): Cytosine in yellow, guanine in green, adenine in red and thymine in blue. Drawing was created by using the Chimera-X software [48]. B: Imino protons region of the 1D NMR titration spectra of LTR-III with BMH-21, recorded at 25 °C and different R = [BMH-21]/[DNA] ratios. C: CD spectra of LTR-III and of the 1:4 mixture with BMH-21 at 20 °C. D: Fitted fraction of folded DNA calculated from the measured ellipticity traces at 284 nm considering a two-state transition.
Fig 5.
Interaction of ST-1968 with the LTR-III structure.
A: The ST-1968/LTR-III complex was obtained by molecular docking and optimized by YASARA Structure [36], and it is represented as side (left) and top (right) views of the ghostly-white solvent-accessible surface (SAS) of the LTR-III target. The ligand was represented as van der Waals (vdW) spheres. The nucleotides are rendered in slabs and filled sugars (left) and mufflers and sugar as tubes (right): Cytosine in yellow, guanine in green, adenine in red and thymine in blue. Drawing was created by using the Chimera-X software [48]. B: Imino protons region of the 1D NMR titration spectra of LTR-III with ST-1968, recorded at 25 °C and different R = [ST-1968]/[DNA] ratios. C: CD spectra of LTR-III and of the 1:4 mixtures with ST-1968 at 20 °C. D: Fitted fraction of folded DNA calculated from the measured ellipticity traces at 284 nm considering a two-state transition.
Fig 6.
Interaction of DOXO with the LTR-III structure.
A: The DOXO/LTR-III complex was obtained by molecular docking and optimized by YASARA Structure [36], and it is represented as side (a, left) and top (a, right) views of the ghostly-white solvent-accessible surface (SAS) of the LTR-III target. The ligand was represented as van der Waals (vdW) spheres. The nucleotides are rendered in slabs and filled sugars left) and mufflers and sugar as tubes (right): Cytosine in yellow, guanine in green, adenine in red and thymine in blue. Drawing was created by using the Chimera-X software [48]. B: Imino protons region of the 1D NMR titration spectra of LTR-III with DOXO, recorded at 25 °C and different R = [DOXO]/[DNA] ratios. C: CD spectra of LTR-III and of the 1:4 mixtures with DOXO at 20 °C. D: Fitted fraction of folded DNA calculated from the measured ellipticity traces at 284 nm considering a two-state transition.
Fig 7.
Aromatic protons region of the 1D NMR titration spectra of LTR-III with DOXO.
Spectra were recorded at 25 °C; R = [DOXO]/[DNA] = 2.0.
Table 1.
Key interactions observed in the LTR-III/ligand complexes as obtained by molecular modeling.
The table shows the nucleotides involved in the interactions together with the type of interactions (HB = Hydrogen Bond).