Structure-Activity Relationships of Novel Tau Ligands: Passive Fibril Binders and Active Aggregation Inhibitors.

ABSTRACT: Intrinsically disordered proteins (IDPs) are core components of many biological processes and are central players in several pathologies. Despite being important drug targets, attempts to design small-molecule ligands that would help understand and attenuate their behavior are frustrated by the structural diversity exhibited by these flexible proteins. To accommodate the dynamic nature of IDPs, we developed a procedure that efficiently identifies active small-molecule ligands for disordered proteins. By exploring the chemical space around these ligands, we refined their effect on aggregation and identified molecular features critical for activity and affinity. Notably, the discovery of this new family of disordered protein ligands was achieved more quickly and with less expense than conven

SUBMITTER: Baggett DW 

PROVIDER: S-EPMC9381419 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature