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What Are We Missing? The Detergent Triton X‐100 Added to Avoid Compound Aggregation Can Affect Assay Results in an Unpredictable Manner
Author(s) -
Ehlert Fabian G. R.,
Linde Kerstin,
Diederich Wibke E.
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700329
Subject(s) - protease , false positive paradox , binding affinities , chemistry , fluorescence , human immunodeficiency virus (hiv) , true positive rate , affinities , computational biology , biochemistry , combinatorial chemistry , biology , enzyme , virology , computer science , machine learning , physics , receptor , quantum mechanics , artificial intelligence
In this study we show that the detergent Triton X‐100, which is widely used in screening campaigns, significantly decreases the binding affinities of some known specific inhibitors of HIV‐1 protease and the well‐established model protease endothiapepsin in a fluorescence‐based assay. Surprisingly, other structurally related inhibitors remain entirely unaffected. As a consequence, those compounds that were affected would most likely have been misclassified as unspecific binders, although they are actually true positives, and thus could be considered excellent starting points for further hit optimization.