High-affinity peptide-based collagen targeting using synthetic phage mimics: From phage display to dendrimer display

(Figure Presented) 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 (Kd = 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. © 2009 American Chemical Society.