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

نویسندگان

  • 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. Lefker
  • Fabien Vincent
  • Lyn H. Jones
  • Hua Xu
  • Lise R. Hoth
  • Kieran F. Geoghegan
  • Xiayang Qiu
  • Mark E. Bunnage
  • Atli Thorarensen
چکیده

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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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2016