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

大环 IL-17A 拮抗剂的结合位点阐明和结构指导设计

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作者:Shenping Liu, Leslie A Dakin, Li Xing, 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 Lefke

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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