Generalized Analysis of Electrophilic Small Molecules
Abstract
ABSTRACT Chemical construction almost universally employs highly customized product‐specific analytics. A transition toward generality will remove this critical bottleneck. Here we present how the fundamental chemical property of electrophilicity can be leveraged to generalize reaction analytics. By using a simple thiol probe we transform customized analytical schemes for electrophilic small molecules into a single generalized readout by tandem mass spectrometry. We apply this strategy to acrylamides commonly found in covalent inhibitors, and subsequently show how it can be extended to other classes of electrophilic small molecules. Application of this approach to high‐throughput chemical synthesis streamlines analysis, enabling rapid readouts of chemical analogs featuring acrylamides.
Article Details
Authors (10)
Uma Neelakantan
Department of Chemical Biology and Therapeutics
Maowei Hu
Department of Chemical Biology and Therapeutics
Jiya Bhatia
Department of Chemical Biology and Therapeutics St. Jude Children's Research Hospital Memphis Tennessee USA
Huyen N. Nguyen
John (Bobby) Yeboah
Department of Chemical Biology and Therapeutics St. Jude Children's Research Hospital Memphis Tennessee USA
Eirinaios I. Vrettos
Department of Chemical Biology and Therapeutics St. Jude Children's Research Hospital Memphis Tennessee USA
Dionysius Copoulos
Department of Chemical Biology and Therapeutics St. Jude Children's Research Hospital Memphis Tennessee USA
Khue N. M. Nguyen
Department of Chemical Biology and Therapeutics St. Jude Children's Research Hospital Memphis Tennessee USA
Madan M. Babu
Center of Excellence for Data Driven Discovery, Department of Structural Biology St. Jude Children's Research Hospital Memphis Tennessee USA
Daniel J. Blair