Functional Promiscuity in C-terminal Peptidic C3aR/C5a1 Ligands — ASN Events
  1. Schedule
  2. Poster Session 1
  3. Functional Promiscuity in C-terminal Peptidic C3aR/C5a1 Ligands

Functional Promiscuity in C-terminal Peptidic C3aR/C5a1 Ligands (#260)

Reena Halai 1 , Meghan L Bellows-Peterson 2 , Will Branchett 3 , James Smadbeck 2 , Chris A Kieslich 2 , Daniel E Croker 1 , Matt A Cooper 1 , Dimitrios Morikis 4 , Trent M Woodruff 5 , Christodoulos A Floudas 2 , Peter N Monk 3
  1. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
  2. Department of Chemical and Biological Engineering, Princeton University, NJ, USA
  3. Department of Infection and Immunity, Sheffield University Medical School, Sheffield, UK
  4. Department of Bioengineering, University of California, Riverside, CA, USA
  5. School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia

Background: 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, C3aR, and C5a1 (C5aR/CD88).

Aims: In this study we used computational methods to design novel C5a1 receptor ligands.

Results: Functional screening in HMDM using the xCELLigence label-free platform demonstrated promiscuity in the specificity of our ligands. No agonist/antagonist activity was observed at C5a1, but we instead saw that some ligands were able to agonize the closely related complement receptor C3aR. This was verified in the presence of C3aR antagonist SB 290157 and in a stable cell line expressing either C5a1 or C3aR alone.

Conclusions: 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.