Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists

Shenping Liu; Leslie Dakin; Xing Li; Jane M. Withka; Parag V. Sahasrabudhe; Wei Li; Mary Ellen Banker; Paul Balbo; Suman Shanker; Boris A. Chrunyk; Zuojun Guo; Jinshan M. Chen; Jennifer A. Young; Guoyun Bai; Jeremy T. Starr; Stephen W. Wright; Joerg Bussenius; Sheng Tan; Ariamala Gopalsamy; Bruce A. Lefker; Fabien Vincent; Lyn H. Jones; Hua Xu; Lise R. Hoth; Kieran F. Geoghegan; Xiayang Qiu; Mark E. Bunnage; Atli Thorarensen

doi:10.1038/srep30859

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Abstract

Interleukin-17A (IL-17A) is a principal driver of multiple inflammatory and immune disorders. Antibodies that neutralize IL-17A or its receptor (IL-17RA) deliver efficacy in autoimmune diseases, but no small-molecule IL-17A antagonists have yet progressed into clinical trials. Investigation of a series of linear peptide ligands to IL-17A and characterization of their binding site has enabled the design of novel macrocyclic ligands that are themselves potent IL-17A antagonists.

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Liu et al. (2016) studied this question.

synapsesocial.com/papers/6a1b7226947c651ddaabe3e3 https://doi.org/10.1038/srep30859

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Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists

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Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists

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