Tyrosine modified analogues of the α4β7 integrin inhibitor biotin-R₈ERY prepared via Click Chemistry: synthesis and biological evaluation

Bioorg Med Chem. 2012 Apr 15;20(8):2638-44. doi: 10.1016/j.bmc.2012.02.035. Epub 2012 Feb 22.


Our continuing programme aiming at developing inhibitors of integrin α4β7, a key mediator of various inflammatory diseases, led us to synthesise a library of cell-permeable peptides based on the biotin-R(8)ERY(∗) template, wherein the tyrosine residue has been modified by using the CuAAC reaction. The peptidomimetics were evaluated in a cell adhesion assay and shown to inhibit Mn(2+)-activated adhesion of mouse TK-1 T cells to mouse MAdCAM-1. Two of the synthesised peptidomimetics, analogues 11 and 14, are more active than our previously reported lead compound biotin-r(9)YDRREY at concentrations of 100 and 50 μM, with 14 exhibiting an IC(50) of less than 10 μM.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotin / chemistry*
  • Cell Line
  • Click Chemistry
  • Dose-Response Relationship, Drug
  • Integrins / antagonists & inhibitors*
  • Mice
  • Models, Biological
  • Molecular Structure
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Structure-Activity Relationship
  • Tyrosine / chemistry*


  • Integrins
  • Oligopeptides
  • integrin alpha4beta7
  • Tyrosine
  • Biotin