NMR applications to find and progress TREX1 binders

Abstract

Inhibition of the exonuclease activity of Three-prime Repair EXonuclease 1 (TREX1) has emerged as a potential novel immunotherapeutic strategy. Herein we describe our screening approach to find initial low-affinity fragment hits for TREX1 from our 19F library and the use of both ligand- and target-based NMR methods for hit confirmation and validation. In a further step to support the early hit expansion stage we describe our setup of a 19F competition assay for KI determination of analogs.

Keywords

• 19F NMR screening
• STD NMR
• 13C precursor protein labeling
• 19F reporter molecule