High-Affinity Peptide-Based Collagen Targeting Using Synthetic Phage Mimics: From Phage Display to Dendrimer Display
High-Affinity Peptide-Based Collagen Targeting Using Synthetic Phage Mimics: From Phage Display to Dendrimer Display
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DOI：
10.1021/ja902285m
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发表时间：
2009-08-26
影响因子：
15
通讯作者：
Meijer, E. W.
中科院分区：
文献类型：
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作者：
Helms, Brett A.;Reulen, Sanne W. A.;Meijer, E. W.
源自噬菌体展示的肽通常表现出比其各自的高亲和力噬菌体显着弱的结合，后者可以以多价方式结合到蛋白质表面。在这里，我们展示了模仿 AB 上噬菌体多价结构的关键方面，树突楔可以将噬菌体展示衍生的胶原结合肽的亲和力增强 100 倍（K-d = 550 nM），从而可以直接可视化天然组织中的胶原结构，其特异性比天然胶原结合蛋白 CNA35 更高。这里介绍的树枝状聚合物展示方法代表了一个明确的、高度通用的平台，用于增强噬菌体展示衍生肽的亲和力，可能具有广泛的适用性。
Peptides derived from phage display typically show significantly weaker binding than their respective high affinity phage, which can bind to protein surfaces in a multivalent fashion. Here we show that mimicking key aspects of the multivalent architecture of the phage on an AB, dendritic wedge can enhance the affinity of a phage-display derived Collagen binding peptide 100-fold (K-d = 550 nM), allowing direct visualization of Collagen architectures in native tissues with a higher specificity than that of the native collagen binding protein CNA35. The dendrimer display approach introduced here represents a well-defined, highly versatile platform for the affinity enhancement of phage display-derived peptides that is likely to be broadly applicable.