Derivation of ligands for the complement C3a receptor from the C-terminus of C5a

Halai, Reena, Bellows-Peterson, Meghan L., Branchett, Will, Smadbeck, James, Kieslich, Chris A., Croker, Daniel E., Cooper, Matthew A., Morikis, Dimitrios, Woodruff, Trent M., Floudas, Christodoulos A. and Monk, Peter N. (2014) Derivation of ligands for the complement C3a receptor from the C-terminus of C5a. European Journal of Pharmacology, 745 176-181. doi:10.1016/j.ejphar.2014.10.041

Author Halai, Reena
Bellows-Peterson, Meghan L.
Branchett, Will
Smadbeck, James
Kieslich, Chris A.
Croker, Daniel E.
Cooper, Matthew A.
Morikis, Dimitrios
Woodruff, Trent M.
Floudas, Christodoulos A.
Monk, Peter N.
Title Derivation of ligands for the complement C3a receptor from the C-terminus of C5a
Journal name European Journal of Pharmacology   Check publisher's open access policy
ISSN 1879-0712
Publication date 2014-12-15
Sub-type Article (original research)
DOI 10.1016/j.ejphar.2014.10.041
Open Access Status DOI
Volume 745
Start page 176
End page 181
Total pages 6
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2015
Language eng
Abstract 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 dysregulation 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 C5a1 (C5aR/CD88). In this study we used computational methods to design novel C5a1 receptor ligands. However, functional screening in human monocyte-derived macrophages using the xCELLigence label-free platform demonstrated altered specificity of our ligands. No agonist/antagonist activity was observed at C5a1, but we instead saw that the ligands 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 C5a1 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.
Keyword C3a receptor
C5a1 receptor
Computational optimization
In silico sequence selection
Label-free screening
Peptide design
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
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