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

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.

SUBMITTER: Liu S

PROVIDER: S-EPMC4985813 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Liu Shenping S Dakin Leslie A LA Xing Li L Withka Jane M JM Sahasrabudhe Parag V PV Li Wei W Banker Mary Ellen ME Balbo Paul P Shanker Suman S Chrunyk Boris A BA Guo Zuojun Z Chen Jinshan M JM Young Jennifer A JA Bai Guoyun G Starr Jeremy T JT Wright Stephen W SW Bussenius Joerg J Tan Sheng S Gopalsamy Ariamala A Lefker Bruce A BA Vincent Fabien F Jones Lyn H LH Xu Hua H Hoth Lise R LR Geoghegan Kieran F KF Qiu Xiayang X Bunnage Mark E ME Thorarensen Atli A

Scientific reports 20160816

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. ...[more]

PMID: 27527709

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