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The role of N- or C-terminal biotinylation in autoantibody recognition of citrullin containing filaggrin epitope peptides in Rheumatoid arthritis

Babos, Fruzsina and Szarka, Eszter and Nagy, György and Majer, Zsuzsa and Sármay, Gabriella and Magyar, Anna and Hudecz, Ferenc (2013) The role of N- or C-terminal biotinylation in autoantibody recognition of citrullin containing filaggrin epitope peptides in Rheumatoid arthritis. Bioconjugate Chemistry, 24 (5). pp. 817-827. ISSN ISSN 1043-1802

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Abstract

Here, we report on the synthesis, conformational analysis and autoantibody binding properties of new sets of Rheumatoid arthritis (RA) specific biotin-peptide conjugates derived from filaggrin epitope peptides. The biotin with or without a linker was attached to the Cit or Arg containing epitope core (311TXGRS315) or epitope region (306SHQESTXGXSXGRSGRSGS324) peptide (where X = Cit), through an amide bond at the N- or C-terminal of the epitopes. Antibody binding was detected by indirect enzyme-linked immunosorbent assay (ELISA) using sera from RA, Systemic lupus erythematosus (SLE) patients as well as healthy individuals and the secondary structure of conjugates was investigated by electronic circular dichroism (ECD). We found that autoantibodies from RA patients recognize specifically both filaggrin epitope region (306SHQESTXGXSXGRSGRSGS324) and short epitope core (311TXGRS315) peptides. Our data also indicate that the positioning of the biotin label within a peptide sequence can markedly influence the antibody binding, but the length of the linker incorporated has essentially no effect on the recognition. ECD experiments demonstrate that the Arg/Cit change does not influence the solution conformation of the peptide conjugates. However, the presence and position of the biotin moiety has a pronounced effect on the conformation of the 5-mer epitope core peptides, while it doesn’t alter the secondary structure of the 19-mer epitope region peptides.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
Depositing User: Dr Katalin Uray
Date Deposited: 28 Jan 2014 08:49
Last Modified: 25 Apr 2014 23:15
URI: http://real.mtak.hu/id/eprint/9292

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