Quadruplex-Duplex Junction: A High-Affinity Binding Site for Indoloquinoline Ligands.

ABSTRACT: A parallel quadruplex derived from the Myc promoter sequence was extended by a stem-loop duplex at either its 5'- or 3'-terminus to mimic a quadruplex-duplex (Q-D) junction as a potential genomic target. High-resolution structures of the hybrids demonstrate continuous stacking of the duplex on the quadruplex core without significant perturbations. An indoloquinoline ligand carrying an aminoalkyl side chain was shown to bind the Q-D hybrids with a very high affinity in the order K_a ≈10⁷  m^-1 irrespective of the duplex location at the quadruplex 3'- or 5'-end. NMR chemical shift perturbations identified the tetrad face of the Q-D junction as specific binding site for the ligand. However, calorimetric analyses revealed significant differences in the thermodyna

SUBMITTER: Vianney YM 

PROVIDER: S-EPMC7756412 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature