biostudies-literatureHarrison RESNEI NIH HHSXSEDENational Institutes of HealthNational Science Foundation1054-1059https://www.ebi.ac.uk/biostudies/studies/S-EPMC7236534biostudies-literatureUnknown11(5)C3d is a hallmark protein of the complement system, whose presence is critical to measure the progression of several immune diseases. Here, we propose to directly target C3d through small peptides mimicking the binding of its natural ligand, the complement regulator Factor H (FH). Through iterative computational analysis and binding affinity experiments, we establish a rationale for the structure-based design of FH-inspired peptides, leading to low-micromolar affinity for C3d and stable binding over microsecond-length simulations. Our FH-inspired peptides call now for further optimization toward high-affinity binding and suggest that small peptides are promising as novel C3d biomarkers and therapeutic tools.ACS medicinal chemistry lettersFactor H-Inspired Design of Peptide Biomarkers of the Complement C3d Protein.PMC7236534TG-MCB160059CHE-1905374R01 EY027440Morikis DNarkhede YBZewde NTHarrison RESPalermo GVullev VIHsu RVfalseFactor H-Inspired Design of Peptide Biomarkers of the Complement C3d Protein.C3d is a hallmark protein of the complement system, whose presence is critical to measure the progression of several immune diseases. Here, we propose to directly target C3d through small peptides mimicking the binding of its natural ligand, the complement regulator Factor H (FH). Through iterative computational analysis and binding affinity experiments, we establish a rationale for the structure-based design of FH-inspired peptides, leading to low-micromolar affinity for C3d and stable binding over microsecond-length simulations. Our FH-inspired peptides call now for further optimization toward high-affinity binding and suggest that small peptides are promising as novel C3d biomarkers and therapeutic tools.2020-01-01T00:00:00Z2020 May2024-10-15T17:06:48.09Z2022-02-10T10:11:44.918ZS-EPMC72365343243542510.1021/acsmedchemlett.9b00663