An Automated Microscale Thermophoresis Screening Approach for Fragment-Based Lead Discovery.

ABSTRACT: Fragment-based lead discovery has proved to be an effective alternative to high-throughput screenings in identifying chemical matter that can be developed into robust lead compounds. The search for optimal combinations of biophysical techniques that can correctly and efficiently identify and quantify binding can be challenging due to the physicochemical properties of fragments. In order to minimize the time and costs of screening, optimal combinations of biophysical techniques with maximal information content, sensitivity, and robustness are needed. Here we describe an approach utilizing automated microscale thermophoresis (MST) affinity screening to identify fragments active against MEK1 kinase. MST identified multiple hits that were confirmed by X-ray crystallography but not detected by

SUBMITTER: Linke P 

PROVIDER: S-EPMC4800460 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature