期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 745, 期 -, 页码 176-181出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2014.10.041
关键词
C3a receptor; C5a(1) receptor; Peptide design; In silico sequence selection; Computational optimization; Label-free screening
资金
- NSF [CTS-0426691, CIS-0427103]
- NIH [5R01GM052032, R24 GM069736]
- Tobacco-Related Disease Research Program [20XT-005]
- US Environmental Protection Agency, EPA [R 832721-010]
- British Heart Foundation [PG/ 09/018/25279]
- US Environmental Agency's STAR program
- DoD, Air Force Office of Scientific Research, and National Defense Science and Engineering Graduate (NDSEG) [32 CFR 168a]
- British Heart Foundation [PG/09/018/25279] Funding Source: researchfish
The complement cascade is a highly sophisticated network of proteins that are well regulated and directed in response to invading pathogens or tissue injury. Complement C3a and C5a are key mediators produced by this cascade, and their clysregulation has been linked to a plethora of inflammatory and autoimmune diseases. Consequently, this has stimulated interest in the development of ligands for the receptors for these complement peptides. C3a receptor. and C5a(1) (C5aR/CD88). In this study we used computational methods to design novel C5a(1) receptor ligands. However, functional screening in human monocyte-derived macrophages using the xCELLigence label-free platform demonstrated altered specificity of our ligands. No agonistfantagonist activity was observed at C5a(1), but we instead saw that the ligancls were able to partially agonize the closely related complement receptor C3a receptor. This was verified in the presence of C3a receptor antagonist SB 290157 and in a stable cell line expressing either C5a(1) or C3a receptor alone. C3a agonism has been suggested to be a potential treatment of acute neutrophil-driven traumatic pathologies, and may have great potential as a therapeutic avenue in this arena. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC B.V license
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据