Searching sequence space for high-affinity binding peptides using ribosome display

J Mol Biol. 2003 May 30;329(2):381-8. doi: 10.1016/s0022-2836(03)00432-7.

Abstract

We present the construction of a synthetic library based on the scaffold of bovine heart fatty acid-binding protein (FABP) with 1.1x10(14) independent members. Ribosome display was applied to select streptavidin-binding peptides in vitro from 2x10(13) molecules of the library each encoding FABP with 15 contiguous random amino acid residues at its N terminus. The selection yielded several different binding peptides. The best binder possessed a dissociation constant as low as 4nM and, in contrast to the previously isolated peptides, contained no HPQ motif. A substitution analysis enabled shortening of the 15-mer peptide and revealed a 9-mer variant with a dissociation constant of 17nM, which is a 1000-fold increase of affinity compared to the already known peptides of this size. This high-affinity binding peptide in combination with the whole set of streptavidin conjugates should be an extremely useful tool for the detection and purification of recombinant proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cattle
  • DNA Primers / chemistry
  • Fatty Acid-Binding Proteins
  • Heart / physiology*
  • In Vitro Techniques
  • Neoplasm Proteins*
  • Oligopeptides / chemistry*
  • Peptide Library
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Streptavidin / metabolism*
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • DNA Primers
  • Fatty Acid-Binding Proteins
  • Neoplasm Proteins
  • Oligopeptides
  • Peptide Library
  • Peptides
  • RNA, Messenger
  • Streptavidin