Affordable Access

Bioactive peptide design based on protein surface epitopes. A cyclic heptapeptide mimics CD4 domain 1 CC' loop and inhibits CD4 biological function.

Authors
  • Satoh, T
  • Aramini, J M
  • Li, S
  • Friedman, T M
  • Gao, J
  • Edling, A E
  • Townsend, R
  • Koch, U
  • Choksi, S
  • Germann, M W
  • Korngold, R
  • Huang, Z
Type
Published Article
Journal
The Journal of biological chemistry
Publication Date
May 02, 1997
Volume
272
Issue
18
Pages
12175–12180
Identifiers
PMID: 9115290
Source
Medline
License
Unknown

Abstract

The interaction between CD4 and major histocompatibility complex class II proteins provides a critical co-receptor function for the activation of CD4(+) T cells implicated in the pathogenesis of a number of autoimmune diseases and transplantation responses. A small synthetic cyclic heptapeptide was designed and shown by high resolution NMR spectroscopy to closely mimic the CD4 domain 1 CC' surface loop. This peptide effectively blocked stable CD4-major histocompatibility complex class II interaction, possessed significant immunosuppressive activity in vitro and in vivo, and strongly resisted proteolytic degradation. These results demonstrate the therapeutic potential of this peptide as a novel immunosuppressive agent and suggest a general strategy of drug design by using small conformationally constrained peptide mimics of protein surface epitopes to inhibit protein interactions and biological functions.

Report this publication

Statistics

Seen <100 times