High-Throughput Optimization of Photochemical Reactions using Segmented-Flow Nanoelectrospray-Ionization Mass Spectrometry.

Autor: Sun AC; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA., Steyer DJ; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA., Robinson RI; Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA., Ginsburg-Moraff C; Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA., Plummer S; Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA., Gao J; Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA., Tucker JW; Medicine Design, Pfizer Inc., Groton, CT 06340, USA., Alpers D; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA., Stephenson CRJ; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA., Kennedy RT; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Jul 10; Vol. 62 (28), pp. e202301664. Date of Electronic Publication: 2023 Apr 18.
DOI: 10.1002/anie.202301664
Abstrakt: Within the realm of drug discovery, high-throughput experimentation techniques enable the rapid optimization of reactions and expedited generation of drug compound libraries for biological and pharmacokinetic evaluation. Herein we report the development of a segmented flow mass spectrometry-based platform to enable the rapid exploration of photoredox reactions for early-stage drug discovery. Specifically, microwell plate-based photochemical reaction screens were reformatted to segmented flow format to enable delivery to nanoelectrospray ionization-mass spectrometry analysis. This approach was demonstrated for the late-stage modification of complex drug scaffolds, as well as the subsequent structure-activity relationship evaluation of synthesized analogs. This technology is anticipated to expand the robust capabilities of photoredox catalysis in drug discovery by enabling high-throughput library diversification.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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