Ferrocenyl glycopeptides as electrochemical probes to detect autoantibodies in multiple sclerosis patients' sera

Glycopeptide analogues of CSF114(Glc), modified at N‐terminus with new ferrocenyl carboxylic acid and a new ferrocenyl‐thiphosphino amino acid, were used to implement a new electrochemical biosensor for autoantibody detection in multiple sclerosis. The ferrocenyl moiety of these “electrochemical probes” did not affect autoantibody recognition both in SP‐ELISA and in inhibition experiments. By electrochemical monitoring the interactions of the modified peptides Fc‐CSF114(Glc) and 4‐FcPhP(S)Abu‐CSF114(Glc) with the autoantibodies, we demonstrated that autoantibodies could be detected with a sensitivity comparable to ELISA method. The new electrochemical probes can be proposed to characterize autoantibodies as biomarkers of multiple sclerosis by a simple, rapid, and reproducible cyclic voltammetry‐based diagnostic methodology. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 488–495, 2008.

[1]  H. Doyle,et al.  Post-translational protein modifications in antigen recognition and autoimmunity. , 2001, Trends in immunology.

[2]  E. Vossenaar,et al.  Anti-CCP antibodies, a highly specific marker for (early) rheumatoid arthritis , 2004 .

[3]  G. Serre.  Autoantibodies to filaggrin/deiminated fibrin (AFA) are useful for the diagnosis and prognosis of rheumatoid arthritis, and are probably involved in the pathophysiology of the disease. , 2001, Joint, bone, spine : revue du rhumatisme.

[4]  F. V. D. van den Hoogen,et al.  Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. , 1998, The Journal of clinical investigation.

[5]  S. Creager,et al.  Dual-stream flow injection method for amplified electrochemical detection of ferrocene derivatives , 2001 .

[6]  E. Novellino,et al.  An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[7]  S. Creager,et al.  Electrochemical reactivity at redox-molecule-based nanoelectrode ensembles , 2001 .

[8]  B. Kolesińska,et al.  A convenient microwave-assisted synthesis of N-glycosyl amino acids , 2007 .

[9]  Monya Baker,et al.  In biomarkers we trust? , 2005, Nature Biotechnology.

[10]  S. Mazzucco,et al.  A synthetic glycopeptide of human myelin oligodendrocyte glycoprotein to detect antibody responses in multiple sclerosis and other neurological diseases. , 1999, Bioorganic & medicinal chemistry letters.

[11]  L. Lesko,et al.  Use of biomarkers from drug discovery through clinical practice: Report of the Ninth European Federation of Pharmaceutical Sciences Conference on Optimizing Drug Development , 2003, Clinical pharmacology and therapeutics.

[12]  J. Durieux,et al.  The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies. , 1995, The Journal of clinical investigation.

[13]  M. Chelli,et al.  Toward biomarkers in multiple sclerosis: new advances , 2006, Expert review of neurotherapeutics.

[14]  M. Porter,et al.  The characteristics of selective heterogeneous electron transfer for optimization of redox recycling amplification systems , 2006 .

[15]  N. Metzler‐Nolte,et al.  Bioorganometallic chemistry of ferrocene. , 2004, Chemical reviews.

[16]  M. Chelli,et al.  Fmoc-protected iminosugar modified asparagine derivatives as building blocks for glycomimetics-containing peptides. , 2007, Bioorganic & medicinal chemistry.

[17]  E. Novellino,et al.  Conformation-activity relationship of designed glycopeptides as synthetic probes for the detection of autoantibodies, biomarkers of multiple sclerosis. , 2006, Journal of medicinal chemistry.

[18]  L. Santoro,et al.  The glycopeptide CSF114(Glc) detects serum antibodies in multiple sclerosis , 2005, Journal of Neuroimmunology.

[19]  Donald D. Johnson,et al.  A concise synthesis of (S)-(−)-3-(2-carboxy-4-pyrrolyl)-alanine , 2000 .

[20]  M. Chelli,et al.  A Convenient Microwave-Enhanced Solid-Phase Synthesis of Difficult Peptide Sequences: Case Study of Gramicidin A and CSF114(Glc) , 2007, International Journal of Peptide Research and Therapeutics.

[21]  P. Lipsky,et al.  Autoantibodies as predictors of disease. , 2001, The Journal of clinical investigation.

[22]  D. Sessler,et al.  Statistically significant , 1999, Nature Medicine.

[23]  M. Chelli,et al.  Peptides as autoimmune diseases antigenic probes: A peptide-based reverse approach to detect biomarkers of autoimmune diseases , 2007 .

[24]  N. Metzler‐Nolte,et al.  Solid‐Phase Synthesis, Characterization, and Antibacterial Activities of Metallocene–Peptide Bioconjugates , 2006, ChemMedChem.

[25]  M. Steward,et al.  An inhibition enzyme immunoassay for estimating relative antibody affinity and affinity heterogeneity. , 1988, Journal of immunological methods.

[26]  S. Creager,et al.  A Signal Amplification Scheme for Ultrasensitive Amperometric Detection in Flowing Streams , 1999 .