Drug Discovery 2022: driving the next life science revolution
Poster
141

The new kids on the block: Fragment screening using Temperature Related Intensity Changes and Grating Coupled Interferometry

Authors

K Shetty1; A O`Keeffe1; C Morton1; T Askwith1; J Wolf1
1 Domainex, UK

Abstract

Biophysical assays have revolutionised the drug discovery process and utilisation of biophysical methods has become increasingly used for hit finding of target classes previously considered as “undruggable”. Fragment screening for hit identification has become increasingly more popular due to significant advances in technology. Domainex has invested in two disruptive technologies that drastically increase the throughput of quantitative, biophysical assays: Grating Coupled Interferometry (Creoptix Wave) and the Dianthus (NanoTemper Technologies).

Creoptix WAVE Delta system uses Grating Coupled Interferometry (GCI). Analogous to Surface Plasmon Resonance (SPR) systems the target protein is immobilised on to specialised sensor chips, however, the laser light travels over the entire length of the chip rather than a single point and the novel fluidics enables measurements of very fast off-rates up to 10 s-1. This increases the sensitivity as more binding events contribute to the overall signal, which is ideal to identify weakly bound fragment hits. The newly launched waveRAPID technology increases system throughput and compound handling time allowing full kinetic characterisation with unattended loading capability for up to 400 compounds in 24 hours.

The Dianthus is a plate-based, in-solution binding assay, which employs Temperature Related Intensity Changes (TRIC) in fluorescence intensity to quantify ligand binding. The Dianthus is suitable for single concentration screening and the determination of true KD values. The sensitivity of the Dianthus pico detector allows for assaying at low nanomolar to high picomolar concentrations of protein, meaning that Dianthus assays can scale in a way many other biophysical approaches cannot. 

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