A diepitopic sequential oligopeptide carrier (SOCn) as mimic of the Sm autoantigen: synthesis, conformation and biological assays

Anti‐Sm (Sm: U1‐U6 RNA‐protein complex) antibodies are usually considered highly specific for systemic lupus erythematosus (SLE), while anti‐U1RNP (U1RNP: U1RNA‐protein complex) are thought of as diagnostic criteria for the mixed connective tissue disease (MCTD). However, both antibody specificities coexist in SLE and MCTD, in varying percentages. Although the anti‐Sm/anti‐U1RNP immunological cross‐reactivity has been initially attributed to a common motif, PPXY(Z)PP (where X, Y, Z are various amino acids), found in the Sm, U1‐A and U1‐C autoantigens, it appears that the conformational features of the Sm epitopes also play an important role in the immunoreactivity. The PPGMRPP and PPGIRGP main epitopes of the Sm antigen were coupled in duplicate to the tetrameric Ac‐(Lys‐Aib‐Gly)4‐OH, SOC4, carrier to form the [(PPGMRPP)2, (PPGIRGP)2]‐SOC4 construct as a mimic of the native Sm. It was found that: (i) the 310 helical structure of SOC4 allows the epitopes to adopt an exposed orientation, similar to their free forms, that facilitates their recognition from the anti‐Sm antibodies, and (ii) the U1‐RNP cross‐reactivity is minimized. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.