Celiacdisease (CD) patients usually present high levels of circulatingIgA antibodies directed to different antigens, in particular tissuetransglutaminase (tTG), gliadin (Glia), and endomysium. A series ofsynthetic peptide constructs containing cross-linked tTG and Gliadeamidated peptides have been synthesized. Peptides were tested inenzyme-linked immunosorbent assays against celiac disease patients’sera versus normal blood donors, and their conformational featureswere evaluated by molecular modeling techniques. Four peptides wererecognized as epitopes by autoantibodies (IgG class) circulating inCD patients’ sera before gluten-free diet. The peptide II, containing Ac-tTG(553–564)-NH2sequencecross-linked with deamidated Ac-α2-Glia(63–71)-NH2, was able to identify specific disease antibodies with asensitivity of 50% and a specificity of 94.4%. Structural conformationsof the linear fragments Ac-tTG(553–564)-NH2andAc-α2-Glia(63–71)-NH2and the correspondingcross-linked peptide IIwere calculated by molecularmodeling. Results showed that cross-linking is determinant to assumeconformations, which are not accessible to the linear fragments. [ABSTRACT FROM AUTHOR]