Vulpetti, Anna, Lingel, Andreas, Dalvit, Claudio, Schiering, Nikolaus, Oberer, Lukas, Henry, Christelle and Lu, Yipin (2022) Efficient Screening of Target-Specific Selected Compounds in Mixtures by 19F NMR Binding Assay with Predicted 19F NMR Chemical Shifts. ChemMedChem : chemistry enabling drug discovery. ISSN 1860-7187; 1860-7179

Abstract

Ligand-based 19F NMR screening is a highly effective and well-established hit-finding approach. The high sensitivity to protein binding makes it particularly suitable for fragment screening. Different criteria can be considered for generating fluorinated fragment libraries. One common strategy is to assemble a large, diverse, well-designed and characterized fragment library which is screened in mixtures, generated based on experimental 19F NMR chemical shifts. Here, we introduce a complementary knowledge-based 19F NMR screening approach, named 19Focused screening, enabling the efficient screening of putative active molecules selected by computational hit finding methodologies, in mixtures assembled and on-the-fly deconvoluted based on predicted 19F NMR chemical shifts. In this study, we developed a novel approach, named LEFshift, for 19F NMR chemical shift prediction using rooted topological fluorine torsion fingerprints in combination with a random forest machine learning method. A demonstration of this approach to a real test case is reported.

Item Type:	Article
Keywords:	Machine learning · 19F NMR screening · 19F NMR chemical shift · Hit finding · Fragment based screening
Date Deposited:	10 Aug 2022 00:46
Last Modified:	10 Aug 2022 00:46
URI:	https://oak.novartis.com/id/eprint/46750