Retro-inverso
peptides which contain NH-CO bonds instead of CO-NH
peptide bonds are much more resistant to proteolysis than L-
peptides. Moreover, they have been shown recently to be able to mimic natural L-
peptides with respect to poly- and
monoclonal antibodies (Guichard, G., Benkirane, N., Zeder-Lutz, G., Van Regenmortel, M. H. V., Briand, J. P., and Muller, S. (1994b) Proc. Natl. Acad. Sci. U.S.A. 91, 9765-9769). We have further tested the capacity of retro-inverso
peptidomimetics to serve as possible targets for
antibodies produced by lupus mice and by patients with rheumatic
autoimmune diseases. Several retro-inverso
peptides corresponding to sequences known to be recognized by
autoantibodies were synthesized, namely
peptides 28-45 and 130-135 of H3, 277-291 of the Ro/SSA 52-kDa
protein, and 304-324 of the Ro/SSA 60-kDa
protein, and tested with autoimmune sera by
enzyme-linked
immunosorbent assay. We have found that retro-inverso
peptides are recognized as well as or even better than natural
peptides by
antibodies from autoimmune patients and lupus mice. This new approach may lead to important progress in the future development of immunodiagnostic assays, particularly in the case of diseases characterized by inflammatory reactions in the course of which the level of degradative
enzymes is increased.