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

被引：16

作者：

Ting, Joey P. ^{[1
]}

Tung, Frances ^{[2
]}

Antonysamy, Stephen ^{[2
]}

Wasserman, Stephen ^{[3
]}

Jones, Spencer B. ^{[4
]}

Zhang, Feiyu F. ^{[2
]}

Espada, Alfonso ^{[5
]}

Broughton, Howard ^{[5
]}

Chalmers, Michael J. ^{[4
]}

Woodman, Michael E. ^{[4
]}

Bina, Holly A. ^{[4
]}

Dodge, Jeffrey A. ^{[4
]}

Benach, Jordi ^{[3
]}

Zhang, Aiping ^{[2
]}

Groshong, Christopher ^{[2
]}

Manglicmot, Danalyn ^{[2
]}

Russell, Marijane ^{[2
]}

Afshar, Sepideh ^{[1
]}

机构：

[1] Eli Lilly Biotechnol Ctr, Dept Prot Engn, San Diego, CA 92121 USA

[2] Eli Lilly & Co, Dept Struct Biol, Lilly Biotechnol Ctr, Discovery Chem Res & Technol, San Diego, CA USA

[3] Eli Lilly & Co, Adv Photon Source, Dept Struct Biol, Discovery Chem Res & Technol, Argonne, IL USA

[4] Lilly Res Labs, Indianapolis, IN USA

[5] Ctr Invest Lilly, Alcobendas, Spain

来源：

PLOS ONE | 2018年 / 13卷 / 01期

关键词：

D O I：

10.1371/journal.pone.0190850

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：18

共 3 条

[1] Phage display as a technology delivering on the promise of peptide drug discovery
Hamzeh-Mivehroud, Maryam
Alizadeh, Ali Akbar
Morris, Michael B.
Church, W. Bret
Dastmalchi, Siavoush
DRUG DISCOVERY TODAY, 2013, 18 (23-24) : 1144 - 1157
[2] Peptide Phage Display as a Tool for Drug Discovery: Targeting Membrane Receptors
Molek, Peter
Strukelj, Borut
Bratkovic, Tomaz
MOLECULES, 2011, 16 (01) : 857 - 887
[3] Mirror-image protein and peptide drug discovery through mirror-image phage display
Qi, Yun-Kun
Zheng, Ji-Shen
Liu, Lei
CHEM, 2024, 10 (08): : 2390 - 2407

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