Unknown

Dataset Information

0

Exploring IDP-Ligand Interactions: tau K18 as A Test Case.


ABSTRACT: Over the past decade intrinsically disordered proteins (IDPs) have emerged as a biologically important class of proteins, many of which are of therapeutic relevance. Here, we investigated the interactions between a model IDP system, tau K18, and nine literature compounds that have been reported as having an effect on tau in order to identify a robust IDP-ligand system for the optimization of a range of biophysical methods. We used NMR, surface plasmon resonance (SPR) and microscale thermophoresis (MST) methods to investigate the binding of these compounds to tau K18; only one showed unambiguous interaction with tau K18. Several near neighbors of this compound were synthesized and their interactions with tau K18 characterized using additional NMR methods, including 1D ligand-observed NMR, diffusion-ordered spectroscopy (DOSY) and 19F NMR. This study demonstrates that it is possible to detect and characterize IDP-ligand interactions using biophysical methods. However, care must be taken to account for possible artefacts, particularly the impact of compound solubility and where the protein has to be immobilized.

SUBMITTER: Vagrys D 

PROVIDER: S-EPMC7432903 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Exploring IDP-Ligand Interactions: tau K18 as A Test Case.

Vagrys Darius D   Davidson James J   Chen Ijen I   Hubbard Roderick E RE   Davis Ben B  

International journal of molecular sciences 20200724 15


Over the past decade intrinsically disordered proteins (IDPs) have emerged as a biologically important class of proteins, many of which are of therapeutic relevance. Here, we investigated the interactions between a model IDP system, tau K18, and nine literature compounds that have been reported as having an effect on tau in order to identify a robust IDP-ligand system for the optimization of a range of biophysical methods. We used NMR, surface plasmon resonance (SPR) and microscale thermophoresi  ...[more]

Similar Datasets

| S-EPMC9417262 | biostudies-literature
| S-EPMC8574012 | biostudies-literature
| S-EPMC10135740 | biostudies-literature
| S-EPMC6187415 | biostudies-literature
| 6520 | ecrin-mdr-crc
| S-EPMC6408985 | biostudies-literature
2024-12-12 | GSE119932 | GEO
| S-EPMC3399554 | biostudies-literature
| S-EPMC4200761 | biostudies-literature
| S-EPMC5928586 | biostudies-literature