Ring Size as an Independent Variable in Cyclooligomeric Depsipeptide Antiarrhythmic Activity.

ABSTRACT: Hit-to-lead studies employ a variety of strategies to optimize binding to a target of interest. When a structure for the target is available, hypothesis-driven structure-activity relationships (SAR) are a powerful strategy for refining the pharmacophore to achieve robust binding and selectivity characteristics necessary to identify a lead compound. Recrafting the three-dimensional space occupied by a small molecule, optimization of hydrogen bond contacts, and enhancing local attractive interactions are traditional approaches in medicinal chemistry. Ring size, however, is rarely able to be leveraged as an independent variable because most hits lack the symmetry required for such a study. Our discovery that the cyclic oligomeric depsipeptide ent-verticilide inhibits mammalian cardiac

SUBMITTER: Smith AN 

PROVIDER: S-EPMC8667307 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature