Structure-Activity Relationship Studies of the Complement Regulator-Recruiting Peptide 5C6
6 affiliations
- 1Department of Pharmaceutical Sciences
- 2University of Basel
- 3Institute for Drug Discovery, Faculty of Medicine
- 4Leipzig University
- 5Perelman School of Medicine
- 6University of Pennsylvania
Abstract
Active recruitment of host complement regulators to biomedical surfaces emerges as a therapeutic strategy to prevent adverse immuno-inflammatory reactions to biomaterials and organ transplants. Coating with the macrocyclic peptide 5C6, which binds and recruits the central complement regulator factor H (FH), was shown to protect clinically relevant surfaces from complement attack. While we previously identified general determinants for the 5C6-FH interaction, more granular structure-activity relationship (SAR) studies have hitherto been missing. In the absence of published target structures, we employed a panel of focused amino acid substitutions combined with biomolecular interaction studies to achieve an SAR profile of 5C6. We identified three positions that are particularly amenable to affinity optimization and combined several changes to produce a next-generation 5C6 analog with enhanced target residence time and serum stability. Biomaterial-related assays suggest that such analogs may confer benefits under stress conditions, providing a path for the further development of 5C6-based coatings.
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BibTeX
@misc{bechtler2026structureactivity,
title = {{Structure-Activity Relationship Studies of the Complement Regulator-Recruiting Peptide 5C6}},
author = {Clément Bechtler and Jannes Felsch and Ekaterina Umnyakova and Lukas Kaufmann and Christina Lamers and John D. Lambris and Daniel Ricklin},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010149/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010149/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Structure-Activity Relationship Studies of the Complement Regulator-Recruiting Peptide 5C6
AU - Clément Bechtler
AU - Jannes Felsch
AU - Ekaterina Umnyakova
AU - Lukas Kaufmann
AU - Christina Lamers
AU - John D. Lambris
AU - Daniel Ricklin
PY - 2026
DA - 2026/10/09
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010149/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010149/v1
AB - Active recruitment of host complement regulators to biomedical surfaces emerges as a therapeutic strategy to prevent adverse immuno-inflammatory reactions to biomaterials and organ transplants. Coating with the macrocyclic peptide 5C6, which binds and recruits the central complement regulator factor H (FH), was shown to protect clinically relevant surfaces from complement attack. While we previously identified general determinants for the 5C6-FH interaction, more granular structure-activity relationship (SAR) studies have hitherto been missing. In the absence of published target structures, we employed a panel of focused amino acid substitutions combined with biomolecular interaction studies to achieve an SAR profile of 5C6. We identified three positions that are particularly amenable to affinity optimization and combined several changes to produce a next-generation 5C6 analog with enhanced target residence time and serum stability. Biomaterial-related assays suggest that such analogs may confer benefits under stress conditions, providing a path for the further development of 5C6-based coatings.
ER -