Factor H-Inspired Design of Peptide Biomarkers of the Complement C3d Protein
Factor H-Inspired Design of Peptide Biomarkers of the Complement C3d Protein
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H 因子启发的补体 C3d 蛋白肽生物标志物的设计
DOI：
10.1021/acsmedchemlett.9b00663
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发表时间：
2020
影响因子：
4.2
通讯作者：
Palermo, Giulia
中科院分区：
文献类型：
--
作者：
Harrison, Reed E.;Zewde, Nehemiah T.;Narkhede, Yogesh B.;Hsu, Rohaine V.;Morikis, Dimitrios;Vullev, Valentine I.;Palermo, Giulia
C3d 是补体系统的标志蛋白，其存在对于测量多种免疫疾病的进展至关重要。在这里，我们建议通过模拟其天然配体补体调节因子 H (FH) 的结合的小肽直接靶向 C3d。通过迭代计算分析和结合亲和力实验，我们为 FH 启发的肽的基于结构的设计建立了基本原理，从而导致 C3d 的低微摩尔亲和力和微秒长度模拟的稳定结合。我们受 FH 启发的肽现在需要进一步优化以实现高亲和力结合，并表明小肽有望作为新型 C3d 生物标志物和治疗工具。
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.