Theory and applications of differential scanning fluorimetry in early-stage drug discovery

Kai Gao, Rick Oerlemans, Matthew R Groves*

*Bijbehorende auteur voor dit werk

Onderzoeksoutputpeer review

62 Citaten (Scopus)
579 Downloads (Pure)

Samenvatting

Differential scanning fluorimetry (DSF) is an accessible, rapid, and economical biophysical technique that has seen many applications over the years, ranging from protein folding state detection to the identification of ligands that bind to the target protein. In this review, we discuss the theory, applications, and limitations of DSF, including the latest applications of DSF by ourselves and other researchers. We show that DSF is a powerful high-throughput tool in early drug discovery efforts. We place DSF in the context of other biophysical methods frequently used in drug discovery and highlight their benefits and downsides. We illustrate the uses of DSF in protein buffer optimization for stability, refolding, and crystallization purposes and provide several examples of each. We also show the use of DSF in a more downstream application, where it is used as an in vivo validation tool of ligand-target interaction in cell assays. Although DSF is a potent tool in buffer optimization and large chemical library screens when it comes to ligand-binding validation and optimization, orthogonal techniques are recommended as DSF is prone to false positives and negatives.

Originele taal-2English
Pagina's (van-tot)85-104
Aantal pagina's20
TijdschriftBiophysical reviews
Volume12
Nummer van het tijdschrift1
Vroegere onlinedatum31-jan.-2020
DOI's
StatusPublished - feb.-2020

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