Bioactive Peptide Design Based on Protein Surface Epitopes

• Published in: The Journal of biological chemistry Vol. 272; no. 18; pp. 12175 - 12180
• Main Authors: Satoh, Takashi, Aramini, James M., Li, Song, Friedman, Thea M., Gao, Jimin, Edling, Andrea E., Townsend, Robert, Koch, Ute, Choksi, Swati, Germann, Markus W., Korngold, Robert, Huang, Ziwei
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 02.05.1997
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.18.12175

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.