Dissecting Dynamic and Hydration Contributions to Sequence-Dependent DNA Minor Groove Recognition.

ABSTRACT: Sequence selectivity is a critical attribute of DNA-binding ligands and underlines the need for detailed molecular descriptions of binding in representative sequence contexts. We investigated the binding and volumetric properties of DB1976, a model bis(benzimidazole)-selenophene diamidine compound with emerging therapeutic potential in acute myeloid leukemia, debilitating fibroses, and obesity-related liver dysfunction. To sample the scope of cognate DB1976 target sites, we evaluated three dodecameric duplexes spanning >10³-fold in binding affinity. The attendant changes in partial molar volumes varied substantially, but not in step with binding affinity, suggesting distinct modes of interactions in these complexes. Specifically, whereas optimal binding was associated with loss

SUBMITTER: Ha VLT 

PROVIDER: S-EPMC7567977 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature