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Deciphering Binding Interactions of IL-23R with HDX-MS: Mapping Protein and Macrocyclic Dodecapeptide Ligands.

ABSTRACT: Molecular characterization of the binding epitope of IL-23R and its cognate cytokine IL-23 is paramount to understand the role in autoimmune diseases and to support the discovery of new inhibitors of this protein-protein interaction. Our results revealed that HDX-MS was able to identify the binding epitope of IL-23R:IL-23, which opened the way to evaluate a peptide macrocycle described in the literature as disrupter of this autoimmune target. Thus, the characterization of the interactions of this chemotype by HDX-MS in combination with computational approaches was achieved. To our knowledge, this is the first reported structural evidence regarding the site where a small compound binds to IL-23R.

SUBMITTER: Sayago C

PROVIDER: S-EPMC6142055 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Deciphering Binding Interactions of IL-23R with HDX-MS: Mapping Protein and Macrocyclic Dodecapeptide Ligands.

Sayago Cristina C Gonzalez Valcarcel Isabel C IC Qian Yuewei Y Lee John J Alsina-Fernandez Jorge J Fite Nathan C NC Carrillo Juan J JJ Zhang Feiyu F FF Chalmers Michael J MJ Dodge Jeffrey A JA Broughton Howard H Espada Alfonso A

ACS medicinal chemistry letters 20180801 9

Molecular characterization of the binding epitope of IL-23R and its cognate cytokine IL-23 is paramount to understand the role in autoimmune diseases and to support the discovery of new inhibitors of this protein-protein interaction. Our results revealed that HDX-MS was able to identify the binding epitope of IL-23R:IL-23, which opened the way to evaluate a peptide macrocycle described in the literature as disrupter of this autoimmune target. Thus, the characterization of the interactions of thi ...[more]

PMID: 30258540

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