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(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.
Helms
Brett A
BA
Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Reulen
Sanne W A
SW
Nijhuis
Sebastiaan
S
de Graaf-Heuvelmans
Peggy T H M
PT
Merkx
Maarten
M
Meijer
E W
EW
D000595:Amino Acid Sequence; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D019151:Peptide Library; D051381:Rats
D050091:Dendrimers; D009842:Oligopeptides; D019151:Peptide Library; D003094:Collagen