Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists
Scientific Reports2016Vol. 6(1), pp. 30859–30859
Citations Over TimeTop 14% of 2016 papers
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
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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