Role of Lipoylation of the Immunodominant Epitope of Pyruvate Dehydrogenase Complex: Toward a Peptide-Based Diagnostic Assay for Primary Biliary Cirrhosis
| Autor: | Feliciana Real-Fernández, Giulia Pacini, Paola Migliorini, Alfonso Carotenuto, Elisa Peroni, Diego Brancaccio, Carlo Selmi, Giuseppina Sabatino, Anna Maria Papini, Francesca Nuti, Maud Larregola, Paolo Rovero, Ettore Novellino, Pier Maria Battezzati, Cedric Rentier |
|---|---|
| Přispěvatelé: | Pacini, Giulia, Carotenuto, Alfonso, Rentier, Cedric, Nuti, Francesca, Real Fernandez, Feliciana, Brancaccio, Diego, Sabatino, Giuseppina, Larregola, Maud, Peroni, Elisa, Migliorini, Paola, Novellino, Ettore, Battezzati, Pier Maria, Selmi, Carlo, Papini, Anna Maria, Rovero, Paolo |
| Rok vydání: | 2015 |
| Předmět: |
Liver Cirrhosis
Lipoylation Immunoenzyme Technique Molecular Conformation Fluorescent Antibody Technique Peptide Enzyme-Linked Immunosorbent Assay Pyruvate Dehydrogenase Complex Epitope Immunoenzyme Techniques Structure-Activity Relationship Primary biliary cirrhosis Antigen Drug Discovery medicine Humans Pyruvate Dehydrogenase (Lipoamide) Antigens chemistry.chemical_classification Primary Biliary Cirrhosis Chemistry Immunodominant Epitopes Liver Cirrhosis Biliary Drug Discovery3003 Pharmaceutical Science Medicine (all) Biliary Autoantibody medicine.disease Pyruvate dehydrogenase complex Molecular biology Peptide-Based Diagnostic Assay Peptides Molecular Medicine Biochemistry Immunodominant Epitope Human |
| Zdroj: | Journal of medicinal chemistry 58 (2015): 6619–6629. doi:10.1021/acs.jmedchem.5b00783 info:cnr-pdr/source/autori:Pacini, Giulia; Carotenuto, Alfonso; Rentier, Cedric; Nuti, Francesca; Real-Fernandez, Feliciana; Brancaccio, Diego; Sabatino, Giuseppina; Larregola, Maud; Peroni, Elisa; Migliorini, Paola; Novellino, Ettore; Battezzati, Pier Maria; Selmi, Carlo; Papini, Anna Maria; Rovero, Paolo/titolo:Role of Lipoylation of the Immunodominant Epitope of Pyruvate Dehydrogenase Complex: Toward a Peptide-Based Diagnostic Assay for Primary Biliary Cirrhosis/doi:10.1021%2Facs.jmedchem.5b00783/rivista:Journal of medicinal chemistry/anno:2015/pagina_da:6619/pagina_a:6629/intervallo_pagine:6619–6629/volume:58 |
| ISSN: | 1520-4804 |
| DOI: | 10.1021/acs.jmedchem.5b00783 |
| Popis: | Primary biliary cirrhosis is an immune-mediated chronic liver disease whose diagnosis relies on the detection of serum antimitochondrial antibodies directed against a complex set of proteins, among which pyruvate dehydrogenase complex is considered the main autoantigen. We studied the immunological role of the lipoyl domain of this protein using synthetic lipoylated peptides, showing that the lipoyl chain chirality does not affect autoantibody recognition and, most importantly, confirming that both lipoylated and unlipoylated peptides are able to recognize specific autoantibodies in patients sera. In fact, 74% of patients sera recognize at least one of the tested peptides but very few positive sera recognized exclusively the lipoylated peptide, suggesting that the lipoamide moiety plays a marginal role within the autoreactive epitope. These results are supported by a conformational analysis showing that the lipoyl moiety of pyruvate dehydrogenase complex appears to be involved in hydrophobic interactions, which may limit its exposition and thus its contribution to the complex antigenic epitope. A preliminary analysis of the specificity of the two most active peptides indicates that they could be part of a panel of synthetic antigens collectively able to mimic in a simple immunoenzymatic assay the complex positivity pattern detected in immunofluorescence. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|