Utilization of peptide phage display to investigate hotspots on IL-17A and what it means for drug discovery.

Autor: Joey P Ting, Frances Tung, Stephen Antonysamy, Stephen Wasserman, Spencer B Jones, Feiyu F Zhang, Alfonso Espada, Howard Broughton, Michael J Chalmers, Michael E Woodman, Holly A Bina, Jeffrey A Dodge, Jordi Benach, Aiping Zhang, Christopher Groshong, Danalyn Manglicmot, Marijane Russell, Sepideh Afshar
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS ONE, Vol 13, Iss 1, p e0190850 (2018)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0190850
Popis: To date, IL-17A antibodies remain the only therapeutic approach to correct the abnormal activation of the IL-17A/IL-17R signaling complex. Why is it that despite the remarkable success of IL-17 antibodies, there is no small molecule antagonist of IL-17A in the clinic? Here we offer a unique approach to address this question. In order to understand the interaction of IL-17A with its receptor, we combined peptide discovery using phage display with HDX, crystallography, and functional assays to map and characterize hot regions that contribute to most of the energetics of the IL-17A/IL-17R interaction. These functional maps are proposed to serve as a guide to aid in the development of small molecules that bind to IL-17A and block its interaction with IL-17RA.
Databáze: Directory of Open Access Journals
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