A Binding Site on IL-17A for Inhibitory Macrocycles Revealed by Hydrogen/Deuterium Exchange Mass Spectrometry

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• 作者：Alfonso Espada ; Howard Broughton ; Spencer Jones ; Michael J. Chalmers ; Jeffrey A. Dodge
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：March 10, 2016
• 年：2016
• 卷：59
• 期：5
• 页码：2255-2260
• 全文大小：366K
• ISSN：1520-4804

文摘

Computational assessment of the IL-17A structure identified two distinct binding pockets, the β-hairpin pocket and the α-helix pocket. The β-hairpin pocket was hypothesized to be the site of binding for peptide macrocycles. Support for this hypothesis was obtained using HDX-MS which revealed protection to exchange only within the β-hairpin pocket. This data represents the first direct structural evidence of a small molecule binding site on IL-17A that functions to disrupt the interaction with its receptor.