High-Affinity Peptide-Based Collagen Targeting Using Synthetic Phage Mimics: From Phage Display to Dendrimer Display

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.