Structure-Activity Relationship Studies of the Complement Regulator-Recruiting Peptide 5C6
Year: 2026
Type: preprint
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.
Source: ChemRxiv
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221130171