Joseph Anacleto, , , Suzanne Ackloo, , , Cheryl Arrowsmith, , , Esther Wolf, , , Yves Leblanc, , , Cristina Lento, , and , Derek J. Wilson*,
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引用次数: 0
Abstract
Conventional bottom-up HDX-MS experiments are highly suitable for use in drug development; however, a major limitation of this approach is that it generally provides only peptide-level structural resolution. Site specific (i.e., single amino acid-resolved) HDX-MS measurements have been achieved using ECD/ETD, but the low efficiency of these fragmentation techniques, combined with poor ion transmission associated with ‘detuning’ the instrument to fully prevent deuterium scrambling, results in sensitivity losses that make ligand binding measurements impractical in a ‘real-world’ (e.g., drug development) context. Here we apply a recently developed method for zero scrambling, high efficiency ECD in the challenging context of ligand binding differential HDX experiments, demonstrating a wealth of additional information that can be acquired when HDX-MS analyses are conducted at the amino acid level.
期刊介绍:
The Journal of the American Society for Mass Spectrometry presents research papers covering all aspects of mass spectrometry, incorporating coverage of fields of scientific inquiry in which mass spectrometry can play a role.
Comprehensive in scope, the journal publishes papers on both fundamentals and applications of mass spectrometry. Fundamental subjects include instrumentation principles, design, and demonstration, structures and chemical properties of gas-phase ions, studies of thermodynamic properties, ion spectroscopy, chemical kinetics, mechanisms of ionization, theories of ion fragmentation, cluster ions, and potential energy surfaces. In addition to full papers, the journal offers Communications, Application Notes, and Accounts and Perspectives