NMR-Based Rational Drug Design of G:G Mismatch DNA Binding Ligand Trapping Transient Complex via Disruption of a Key Allosteric Interaction.

ABSTRACT: Small molecules that bind to mismatched DNA have been applied in various fields, including nanotechnology, bioimaging, and therapeutics. However, the intrinsic dynamic nature of mismatched DNA complicates the prediction of structural changes upon ligand binding, hindering rational ligand design. In this study, NMR was used for structure-based drug design, with a focus on the G:G mismatch binder ND and the structural dynamics of the DNA-ND complex. Through comprehensive NMR analysis with isotope labeling, two complex structures, the transient and stable complexes, were successfully determined. The nucleobase flip-outs and the distortion of the phosphate backbone of the complex structures were characterized by residual dipolar coupling (RDC) and ³¹P NMR, respectively

SUBMITTER: Sakurabayashi S 

PROVIDER: S-EPMC12046557 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature