Microperoxidase-11-induced reconfiguration of G-quadruplex nanostructures

The controlled manipulation of the secondary structure of guanine quadruplexes (GQs) using ligands has been extensively employed in the field of DNA biotechnology. However, there is little predictability for such processes based on the sequence of the DNA target. Herein, we explored the impact of GQ sequence identity on the kinetics of this chaperone-like binding mechanism and its influence on subsequent sequence preference. We monitored the topological conversion of flexible, non-parallel GQs, encoding for two iso-compositional groups, that is induced by the microperoxidase-11 ligand. We found that within each group of GQs, the activation energy for the binding process is linearly related to the melting temperature of the individual sequences, regardless of their composition or topology. These results shed light on the chaperone-like mechanism and open new avenues for designing ligands with sequence specificity based on such mechanisms.