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Factor H‑Inspired Design of Peptide Biomarkers of the Complement C3d Protein
journal contribution
posted on 2020-03-05, 14:41 authored by Reed E.
S. Harrison, Nehemiah T. Zewde, Yogesh B. Narkhede, Rohaine V. Hsu, Dimitrios Morikis, Valentine I. Vullev, Giulia PalermoC3d
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.