Helms Brett A, Reulen Sanne W A, Nijhuis Sebastiaan, de Graaf-Heuvelmans Peggy T H M, Merkx Maarten, Meijer E W
Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
J Am Chem Soc. 2009 Aug 26;131(33):11683-5. doi: 10.1021/ja902285m.
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(5) 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.
源自噬菌体展示的肽通常显示出比其各自的高亲和力噬菌体明显更弱的结合力，后者能够以多价方式结合到蛋白质表面。在这里我们表明，在一个AB(5)树枝状楔形物上模拟噬菌体多价结构的关键方面，可以将源自噬菌体展示的胶原结合肽的亲和力提高100倍（解离常数K(d)=550 nM），从而能够以比天然胶原结合蛋白CNA35更高的特异性直接可视化天然组织中的胶原结构。这里介绍的树枝状聚合物展示方法代表了一个定义明确、高度通用的平台，用于增强源自噬菌体展示的肽的亲和力，这可能具有广泛的适用性。
