title: HDX-MS guided drug discovery: small molecules and biopharmaceuticals.
abstract: Hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS or DXMS) has emerged as an important tool for the development of small molecule therapeutics and biopharmaceuticals. Central to these advances have been improvements to automated HDX-MS platforms and software that allow for the rapid acquisition and processing of experimental data. Correlating the HDX-MS profile of large numbers of ligands with their functional outputs has enabled the development of structure activity relationships (SAR) and delineation of ligand classes based on functional selectivity. HDX-MS has also been applied to address many of the unique challenges posed by the continued emergence of biopharmaceuticals. Here we review the latest applications of HDX-MS to drug discovery, recent advances in technology and software, and provide perspective on future outlook.
authors.affiliation: Molecular Therapeutics Department, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, United States.
authors.forename: David P
authors.initials: DP
authors.lastname: Marciano
authors.affiliation: Molecular Therapeutics Department, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, United States.
authors.forename: Venkatasubramanian
authors.initials: V
authors.lastname: Dharmarajan
authors.affiliation: Molecular Therapeutics Department, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, United States. Electronic address: pgriffin@scripps.edu.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Griffin
mesh_terms: D003903:Deuterium / Q000737:chemistry*; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D006859:Hydrogen / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods* / Q000639:trends; D004364:Pharmaceutical Preparations / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D006859:Hydrogen; D003903:Deuterium