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

J Med Chem

Lilly Research Laboratories, Eli Lilly and Company , Indianapolis, Indiana 46285, United States.

Published: March 2016

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.

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http://dx.doi.org/10.1021/acs.jmedchem.5b01693DOI Listing

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