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The CD4-MHC class ƒ¹ ƒ¹ interaction is critical for the activation of CD4⁺ T cells(1) which participate in the pathogenesis of a number of immune-based human conditions, including autoimmune diseases and organ transplant rejections. In this study, they have designed a small synthetic cyclic heptapeptide (cyclo(CNSNQIC)) derived from the CC` loop(amino acid 30-34) of human CD4 domain 1(2,3). According to the high resolution NMR spectroscopy, the structure of the cyclic peptide closely mimics the native CD4 D1 CC` surface epitopes. Then they showed that this peptide effectively inhibit the CD4-MHC class ƒ¹ ƒ¹ interaction, exhibited significant immunosuppressive activity in vitro and in vivo, and was not favorable for proteolytic recognition. Thus, they demonstrated this cyclic peptide possessed therapeutic potential as a novel immunosuppressive agent. Furthermore, they also showed a general strategy of bioactive drug design based on protein surface epitopes.(4)

1. Doyal, C., and Strominger, J. L. (1987) Nature 330,256-259.
2. Wang, J., Yan, Y., Garrett, T. P. J., Liu, J., Rodger, D. W., Garlick, R. L., Tarr, G. E., Husain, Y., Reinherz, E. L., and Harrison, S. C. (1990) Nature 348, 411-418.
3. Fleury, S., Lamarre, D., Meloche, S., Ryu, S.-E., Cantin. C.,Hendrickson, W. A., and Sekaly, R. P. (1991) Cell 66,1037-1049.
4. (Source)Satoh, T., Aramini, J. M., Li, S., Friedman, T. M., Gao, J., (1997) J. Biol. Chem. 272, 12175-12180.