Factor H-Inspired Design of Peptide Biomarkers of the Complement C3d Protein.

Autor:	Harrison RES; Department of Bioengineering and Department of Chemistry, University of California Riverside, 900 University Avenue, Riverside California 92507, United States., Zewde NT; Department of Bioengineering and Department of Chemistry, University of California Riverside, 900 University Avenue, Riverside California 92507, United States., Narkhede YB; Department of Bioengineering and Department of Chemistry, University of California Riverside, 900 University Avenue, Riverside California 92507, United States., Hsu RV; Department of Bioengineering and Department of Chemistry, University of California Riverside, 900 University Avenue, Riverside California 92507, United States., Morikis D; Department of Bioengineering and Department of Chemistry, University of California Riverside, 900 University Avenue, Riverside California 92507, United States., Vullev VI; Department of Bioengineering and Department of Chemistry, University of California Riverside, 900 University Avenue, Riverside California 92507, United States., Palermo G; Department of Bioengineering and Department of Chemistry, University of California Riverside, 900 University Avenue, Riverside California 92507, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Feb 28; Vol. 11 (5), pp. 1054-1059. Date of Electronic Publication: 2020 Feb 28 (Print Publication: 2020).
DOI:	10.1021/acsmedchemlett.9b00663
Abstrakt:	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. Competing Interests: The authors declare no competing financial interest. (Copyright © 2020 American Chemical Society.)
Databáze:	MEDLINE
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