Managing Experimental 3D Structures in the Beyond-Rule-of-5 Chemical Space: The Case of Rifampicin.

ABSTRACT: The beyond-Rule-of-5 (bRo5) chemical space is a source of new oral drugs and includes large and flexible compounds. Because of their size and conformational variability, bRo5 molecules assume different privileged conformations in the compartments of human body, i. e., they can exhibit chameleonic properties. The elucidation of the ensemble of 3D structures explored by such molecules under different conditions is therefore critical to check the role played by chameleonicity to modulate cell permeability. Here we characterized the conformational ensembles of rifampicin, a bRo5 drug, in polar and nonpolar solvents and in the solid state. We performed NMR experiments, analyzed their results with a novel algorithm and set-up a pool of ad hoc in silico strategies to investigate crystallographic

SUBMITTER: Ermondi G 

PROVIDER: S-EPMC8361677 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature