Combination of MS Binding Assays and affinity selection mass spectrometry for screening of structurally homogenous libraries as exemplified for a focused oxime library addressing the neuronal GABA transporter 1

Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products

“…These classical MS methods are most commonly used for the investigation of enzyme kinetics; however, Gabriel et al recently combined MS binding assays with affinity-selection MS for an activity-based drug discovery screen. 80,81 This study exploited structural insights into GAT1 inhibitors gamma aminobutyric acid (GABA) and (R)-nipecotic acid to explore the membrane transport protein, GABA transporter type 1 (GAT1). Toward this end, a derivative of nipecotic acid was reacted with a library of aldehydes to form oximes; these oximes were then identied by their tag using multiple reaction monitoring (MRM) MS experiments.…”