Novel peptide ligands for integrin alpha 6 beta 1 selected from a phage display library

J Biochem. 1996 Aug;120(2):445-51. doi: 10.1093/oxfordjournals.jbchem.a021431.

Abstract

Integrin alpha 6 beta 1 is a major adhesion receptor for the basement membrane, specifically binding to laminin-1. To identify the peptide sequences recognized by alpha 6 beta 1, we screened a 15-mer phage display library by panning with alpha 6 beta 1 purified from human placenta. DNA sequencing of 73 randomly picked phage revealed that three clones were dominantly enriched after repeated panning with alpha 6 beta 1. None of the peptide sequences displayed on these phage showed significant homology to laminin-1. A synthetic peptide modeled after the sequence displayed by one of these phage, designated P3, was found to strongly inhibit the binding of laminin-1 to alpha 6 beta 1. This inhibitory effect of the P3 peptide seems to be specific for alpha 6 beta 1, since it did not affect the binding of fibronectin to integrin alpha 5 beta 1. A synthetic peptide with a scrambled P3 amino acid sequence barely inhibited the binding of laminin-1 to alpha 6 beta 1. When coated on a substratum after conjugation with bovine serum albumin, the P3 peptide was capable of promoting cell spreading in an alpha 6 beta 1-dependent manner, although the peptide with the scrambled sequence showed activity similar to that of a control peptide. These results taken together indicate that the P3 peptide is a novel ligand for integrin alpha 6 beta 1 with potent cell spreading activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacteriophages
  • Cattle
  • Cell Adhesion / drug effects
  • Female
  • Humans
  • Integrin alpha6beta1
  • Integrins / antagonists & inhibitors
  • Integrins / isolation & purification
  • Integrins / metabolism*
  • Ligands
  • Molecular Sequence Data
  • Peptide Library
  • Peptides / chemistry
  • Peptides / metabolism*
  • Peptides / pharmacology
  • Placenta / immunology
  • Pregnancy
  • Rats
  • Tumor Cells, Cultured

Substances

  • Integrin alpha6beta1
  • Integrins
  • Ligands
  • Peptide Library
  • Peptides