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

J Am Chem Soc. 2009 Aug 26;131(33):11683-5. doi: 10.1021/ja902285m.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / metabolism*
  • Collagen / chemistry
  • Collagen / metabolism*
  • Dendrimers / chemistry*
  • Dendrimers / metabolism*
  • Models, Molecular
  • Molecular Conformation
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Peptide Library*
  • Rats

Substances

  • Dendrimers
  • Oligopeptides
  • Peptide Library
  • Collagen