Leonhard Geist, Paola Martinelli, Shereena Mohideen-Ali, Patrick Werni, Gerhard Fischer, Julian E. Fuchs, Klaus Rumpel, Moriz Mayer
{"title":"NMR applications to find and progress TREX1 binders","authors":"Leonhard Geist, Paola Martinelli, Shereena Mohideen-Ali, Patrick Werni, Gerhard Fischer, Julian E. Fuchs, Klaus Rumpel, Moriz Mayer","doi":"10.1016/j.jmro.2022.100075","DOIUrl":null,"url":null,"abstract":"<div><p>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 <sup>19</sup>F 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 <sup>19</sup>F competition assay for <em>K<sub>I</sub></em> determination of analogs.</p></div>","PeriodicalId":365,"journal":{"name":"Journal of Magnetic Resonance Open","volume":null,"pages":null},"PeriodicalIF":2.6240,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Magnetic Resonance Open","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666441022000450","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.