Detection of Small-Molecule Aggregation with High-Throughput Microplate Biophysical Methods.

Current Protocols in Chemical Biology
Samantha J AllenKevin J Lumb

Abstract

Small-molecule drug discovery can be hindered by the formation of aggregates that act as non-selective inhibitors of drug targets. Such aggregates appear as false positives in high-throughput screening campaigns and can bedevil structure-activity relationships during compound optimization. Protocols are described for resonant waveguide grating (RWG) and dynamic light scattering (DLS) as microplate-based high-throughput approaches to identify compound aggregation. Resonant waveguide grating and dynamic light scattering give equivalent results for the compound test set, as assessed with Bland-Altman analysis. © 2019 The Authors. Basic Protocol 1: Resonant waveguide grating (RWG) in 384-well or 1536-well plate format to detect compound aggregation Basic Protocol 2: Dynamic light scattering (DLS) in 384-well plate format to detect compound aggregation.

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Citations

Mar 25, 2021·Journal of Medicinal Chemistry·Parnian LakBrian K Shoichet

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