Autoimmunità

Meccanismi molecolari della Sclerosi Multipla
Responsabili scientifici: M. Chelli, F. Lolli, A.M. Papini, P. Rovero

Il progetto di punta di PeptLab è diretto allo sviluppo di nuovi glicopeptidi utili per la diagnosi ed il trattamento della Sclerosi Multipla, una grave malattia del sistema nervoso.

Sottoprogetti:

• Studio di epitopi peptidici coinvolti nel riconoscimento di autoanticorpi anti-CSF114(Glc) nella Sclerosi Multipla (F. Nuti).
• Messa a punto di un approccio chimico inverso per lo sviluppo di CSF114(Glc) (G. Sabatino).
• Sviluppo di nuove tecniche per rivelare la presenza di anticorpi nel siero di pazienti affetti da Sclerosi Multipla (E. Peroni).
• Approccio bio-informatico allo sviluppo di nuove sonde antigeniche sintetiche specifiche per la Sclerosi Multipla (M.C. Alcaro e F. Nuti).
• Studi di tipo proteomico per l’identificazione di antigeni nativi nella Sclerosi Multipla (M.C. Alcaro).
• Studio del ruolo di cellule B memoria nel riconoscimento di autoanticorpi anti-CSF114(Glc) nella Sclerosi Multipla (F. Lolli).
• Sintesi e semi-sintesi di proteine glicosilate per la caratterizzazione di antigeni nativi della Sclerosi Multipla (F. Gori).

Tali prodotti sono stati brevettati nel 2001 dall’Università di Firenze [Brevetto italiano FI 2001A000114 del 22.06.2001. Autori: A.M. Papini, M. Chelli, P. Rovero, F. Lolli. Proprietà: Università di Firenze. International Patent application WO 03/000733] e sono attualmente oggetto di trasferimento tecnologico.
Fin dal 2004, questa ricerca è stata cofinanziata dall' Ente Cassa di Risparmio di Firenze.

Pubblicazioni recenti su riviste ISI:

F. Lolli, B. Mulinacci, A. Carotenuto, B. Bonetti, G. Sabatino, B. Mazzanti, A.M. D’Ursi, E. Novellino, M. Pazzagli, L. Lovato, M.C. Alcaro, E. Peroni, M.C. Pozo-Carrero, F. Nuti, L. Battistini, G. Borsellino, M. Chelli, P. Rovero, A.M. Papini
An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of Multiple Sclerosis
Proc. Natl. Acad. Sci. USA (2005) 102, 10273-10278.

F. Lolli, B. Mazzanti, M. Pazzagli, E. Peroni, M.C. Alcaro, G. Sabatino, R. Lanzillo, V. Brescia Morra, L. Santoro, C. Gasperini, S. Galgani, M.M. D’ Elios, V. Zipoli, S. Sotgiu, M. Pugliatti, P. Rovero , M. Chelli, A.M. Papini
The glycopeptide CSF114(Glc) detects serum antibodies in multiple sclerosis.
J. Neuroimmunol. (2005) 167, 131-137.

F. Lolli, P. Rovero, M. Chelli, A.M. Papini
Toward biomarkers in multiple sclerosis: new advances.
Expert Rev. Neurotherapeutics (2006) 6, 781-794.

A. Carotenuto, A.M. D’Ursi, B. Mulinacci, I. Paolini, F. Lolli, A.M. Papini, E. Novellino, and P. Rovero.
Conformation-activity relationship of designed glycopeptides as synthetic probes for the detection of autoantibodies, biomarkers of multiple sclerosis.
J. Med. Chem. (2006) 49, 5072-5079.

M.C. Alcaro, A.M. Papini.
Contribution of peptides to multiple sclerosis research.
Biopolymers (2006) 84, 4, 349-67.

M.C. Alcaro, F. Lolli, P. Migliorini, M. Chelli, P. Rovero, and A.M. Papini.
Peptides as autoimmune diseases antigenic probes: a peptide-based reverse approach to detect biomarkers of autoimmune diseases.
Chemistry Today (2007) 25, 3, 14-16.

F. Nuti, I. Paolini, F. Cardona, M. Chelli, F. Lolli, A. Brandi, A. Goti, P. Rovero,  A.M. Papini.
Fmoc-protected iminosugar modified asparagine derivatives as building blocks for glycomimetics-containing peptides.
Bioorg. Med. Chem. (2007) 15, 3965-3973.

F. Rizzolo, G. Sabatino, M. Chelli, P. Rovero,  A.M. Papini
A convenient microwave-enhanced solid-phase synthesis of difficult sequences: case study of gramicidin A and CSF114(Glc).
Int. J. Pept. Res. Ther. (2007) 13, 1-2, 203-208.

V.V. Volkov, R. Chelli, W. Zhuang, F. Nuti, Y. Takaoka, A.M. Papini, S. Mukamel, and R. Righini.
Electrostatic interactions in phospholipid membranes revealed by coherent two-dimensional infrared spectroscopy.
Proc. Natl. Acad. Sci., U.S.A. (2007) 104, 15323-15327.

F. Real Fernández, A. Chamois-Colson, J. Bayardon, F. Nuti, E. Peroni, R. Meunier-Prest, F. Lolli, M. Chelli, C. Darcel, S. Jugè, and A.M. Papini.
Ferrocenyl Glycopeptides as Electrochemical Probes to Detect Autoantibodies in Multiple Sclerosis Patients’ Sera.
Biopolymers (Peptide Science) (2008) 90, 4, 488-495.

A. Carotenuto, M.C. Alcaro, M.R. Saviello, E. Peroni, F. Nuti, A.M. Papini, E. Novellino, and P. Rovero.
Designed glycopeptides with different b-turn types as synthetic probes for the detection of autoantibodies, biomarkers of Multiple Sclerosis.
J. Med. Chem. (2008), 51, 5304–5309.

S. Carganico, P. Rovero, J.A. Halperin, A.M. Papinia, and M. Chorev.
Building blocks for the synthesis of post-translationally modified glycated peptides and proteins.
J. Pept. Sci. (2009) 15, 67-71.

M.A. Bonache, F. Nuti, A. Le Chevalier Isaad, F. Real-Fernández, M. Chelli, P. Rovero and A.M. Papini.
Synthesis of new ribosylated Asn building blocks as useful tools for glycopeptide and glycoprotein synthesis.
Tetrahedron Letters (2009) 50, 4151-4153.

A.M. Papini. The use of post-translationally modified peptides for detection of biomarkers of immune-mediated diseases. J. Pept. Sci. (2009), 15, 621-628.

M.A Bonache, A. Le Chevalier, F. Nuti, E. Peroni, M. Chelli, P. Rovero, and A.M. Papini. Ribose building block for the synthesis of glycopeptides for fishing out antibodies in autoimmune diseases. Adv. Exp. Med. Biol. (2009)

F. Real-Fernández, F. Nuti, M.A. Bonache, M. Boccalini, S. Chimichi, M. Chelli, and A.M. Papini. Microwave-assisted reaction of glycosylamine with aspartic acid. Amino Acids (2010) 39, 599-604.

F. Nuti, E. Peroni, F. Real-Fernández, M.A. Bonache, A. Le Chevalier-Isaad, M. Chelli, N. Lubin-Germain, J. Uziel, P. Rovero, F. Lolli, and A.M. Papini. Post-translationally modified peptides efficiently mimicking neo-antigens: a challenge for theragnostics of autoimmune diseases. Biopolymers: Peptide Science (2010) 94, 6, 791-799.

F. Gori, B. Mulinacci, L. Massai, C. Avolio, M. Caragnano, E. Peroni, S. Lori, M. Chelli, A.M. Papini, P. Rovero, F. Lolli. IgG and IgM antibodies to the refolded MOG(1-125) extracellular domain in humans. J. Neuroimmunol. (2011) 233, 216-220.

Altre pubblicazioni recenti:

M.C. Alcaro, E. Naldini, B. Mulinacci, B. Mazzanti, M. Pazzagli, E. Peroni, M. Chelli, P. Rovero, A.M. Papini.
Identification of new autoantigens in Multiple Sclerosis by glycopeptide libraries.
In: Peptides 2004. Bridges Between Disciplines. M. Flegel, M. Fridkin, C. Gilon, J. Slaninova (Eds), Kenes International, Geneva, Switzerland (2005), pp. 374-375.

B. Mulinacci, I. Paolini, A. Carotenuto, B. Mazzanti, M. Pazzagli, M. Chelli, F. Lolli, P. Rovero, A.M. Papini.
Beta-Hairpin glycopeptides as mimetic autoantigens in multiple sclerosis.
In: Peptides 2004. Bridges Between Disciplines. M. Flegel, M. Fridkin, C. Gilon, J. Slaninova (Eds), Kenes International, Geneva, Switzerland (2005), pp. 593-594.

E. Peroni, F. Peri, F. Nuti, M. Chelli, A.M. Papini.
Synthetic strategies for forming the glycan-peptide linkage.
In: Peptides 2004. Bridges Between Disciplines. M. Flegel, M. Fridkin, C. Gilon, J. Slaninova (Eds), Kenes International, Geneva, Switzerland (2005), pp. 599-600.

M.C. Alcaro, F. Barbetti, F. Nuti, F. Real-Fernandez, B. Mazzanti, M. Chelli, P. Rovero, A.M. Papini.
Optimization of Multiple Sclerosis Antigenic Probes by a Combinatorial Approach.
In: Understanding Biology Using Peptides. S.E. Blondelle (Ed.), American Peptide Society, San Diego, USA (2006), pp. 779-780.

F. Nuti, I. Paolini, E. Peroni, F. Real-Fernandez, M. Pazzagli, M.C. Pozo-Carrero, F. Lolli, M. Chelli, P. Rovero, A.M. Papini.
Does an Aberrant Glucosylation Trigger Autoimmunity in Multiple Sclerosis?
In: Understanding Biology Using Peptides. S.E. Blondelle (Ed.), American Peptide Society, San Diego, USA (2006), pp. 775-776.

E.S. Bulukin, E. Peroni, M. Minunni, M. Pazzagli, P. Rovero, M. Mascini, A.M. Papini.
Development of an Efficient Multiple Sclerosis Diagnostic Technology Based on an Optical Glycopeptide Immunosensor.
In: Understanding Biology Using Peptides. S.E. Blondelle (Ed.), American Peptide Society, San Diego, USA (2006), pp. 785-786.

B. Mulinacci, C. Breithaupt, P.P. Pal, N. Budisa, M. Pazzagli, B. Mazzanti, P. Rovero, L. Moroder, A.M. Papini.
Cross-reactivity studies of rMOGED with synthetic putative autoantigens CSF114(Glc) and [N31(Glc)]hMOG(30-50) in Multiple Sclerosis patients’ sera.
In: Understanding Biology Using Peptides. S.E. Blondelle (Ed.), American Peptide Society, San Diego, USA (2006), pp. 769-770.

I. Paolini, F. Nuti, E. Peroni, F. Lolli, M. Chelli, P. Rovero, A.M. Papini.
An universal peptide scaffold to develop antigenic probes specific for autoimmune diseases.
In: Peptides 2006. K. Rolka, P. Rekowski, J. Silberring (Eds.), Kenes International, Geneva, Switzerland (2007), pp 672-673.

M.C. Alcaro, A. Carotenuto, C. Bonaccini, B. Mulinacci, G. Bonechi, F. Lolli, M. Chelli, P. Gratteri, A. Tramontano, E. Novellino, A.M. Papini, P. Rovero.
Conformationally driven rational design of glycopeptides as synthetic probes for the detection of autoantibodies, biomarkers of multiple sclerosis.
In: Peptides 2006. K. Rolka, P. Rekowski, J. Silberring (Eds.), Kenes International, Geneva, Switzerland (2007), pp 684-685.

F. Nuti, E. Peroni, E.S. Bulukin, M. Minunni, B. Mulinacci, M. Chelli, M. Mascini, P. Rovero, A.M. Papini.
Improvement of autoantibody detection in autoimmune diseases by innovative solid-phase glycopeptide based technologies.
In: Peptides 2006. K. Rolka, P. Rekowski, J. Silberring (Eds.), Kenes International, Geneva, Switzerland (2007), pp 588-589

M.A. Bonache, F. Nuti, A. Le Chevalier Isaad, E. Peroni, M. Chelli, P. Rovero, A.M. Papini. New Building Blocks Useful For The Synthesis Of Ribosylated Peptides. In Peptides 2008: The Proceedings of the 30th European Peptide Symposium. H. Lankinen, J. Vallivirta, T. Strandin, J. Hepojoki (Eds.) 2008. pp 188-189. ISBN 978-952-92-5198-8.

F. Nuti, N. Qvit, F. Rizzolo, M. Hurevich, E. Peroni, M. Chelli, P. Rovero, C. Gilon, A.M. Papini. Microwave-Assisted Solid Phase Synthesis of Backbone Cyclic Glycopeptide Libraries. In Peptides 2008: The Proceedings of the 30th European Peptide Symposium. H. Lankinen, J. Vallivirta, T. Strandin, J. Hepojoki (Eds.) 2008. pp 278-279. ISBN 978-952-92-5198-8.

A.M. Papini. Peptide-based immunoassays for biomarkers detection: a challenge for translational research. In Peptides 2008: The Proceedings of the 30th European Peptide Symposium. H. Lankinen, J. Vallivirta, T. Strandin, J. Hepojoki (Eds.) 2008. pp 438-439. ISBN 978-952-92-5198-8.

F. Gori, B. Mulinacci, A.M. Papini, P. Rovero, and A.G. Beck-Sickinger. Semi-synthetic approaches to glycosylation of MOG as autoantigen in Multiple Sclerosis disease. In Peptides 2008: The Proceedings of the 30th European Peptide Symposium. H. Lankinen, J. Vallivirta, T. Strandin, J. Hepojoki (Eds.) 2008. pp 444-445. ISBN 978-952-92-5198-8.

E. Innocenti, E. Peroni, F. Nuti, M. Chelli, P. Rovero, C. Selmi and A. M. Papini. Post translational modified peptide-based ELISA to detect autoantibodies in Primary Biliary Cirrhosis. In Peptides 2008: The Proceedings of the 30th European Peptide Symposium. H. Lankinen, J. Vallivirta, T. Strandin, J. Hepojoki (Eds.) 2008. pp 470-471. ISBN 978-952-92-5198-8.

M.C. Alcaro, A. Carotenuto, F. Nuti, I. Paolini, E. Peroni, G. Sabatino, E. Novellino, F. Lolli, A.M. Papini, and P. Rovero. Modified peptides for the diagnosis of autoimmune diseases. New Perspective in Medicinal Chemistry (2009), Vol. 1: 149-158.

E. Peroni, M. Tontini, B. Mulinacci, M. Chelli, F. Lolli, P. Rovero, and A.M. Papini. A Glycopeptide-based Technique for Selective Antibodies Purification. In: Peptides for Youth: The Proceedings of the 20th American Peptide Symposium S. Del Valle, E. Escher, W.D. Lubell (Eds.), Springer (2009), pp. 369-370. ISBN: 978-0-387-73656-3.

M.A. Bonache, A. Le Chevalier, F. Nuti, E. Peroni, M. Chelli, P. Rovero, and A.M. Papini. Ribose Building Block For The Synthesis Of Glycopeptides For Fishing Out Antibodies In Autoimmune Diseases. In: Peptides for Youth: The Proceedings of the 20th American Peptide Symposium S. Del Valle, E. Escher, W.D. Lubell (Eds.), Springer (2009), pp. 441-442. ISBN: 978-0-387-73656-3.

F. Nuti, B. Mulinacci, E. Peroni, M.C. Alcaro, I. Paolini, F. Benedetti, A. Carotenuto, F. Ciolli, F. Lolli, M. Chelli, P. Rovero, and A.M. Papini. Studies for Identification of the Minimal Epitope(s) mimicked by the Synthetic Glucopeptide CSF114(Glc). In: Peptides for Youth: The Proceedings of the 20th American Peptide Symposium S. Del Valle, E. Escher, W.D. Lubell (Eds.), Springer (2009), pp. 431-432. ISBN: 978-0-387-73656-3

F. Gori, B. Mulinacci, E. Bonchi, M. Chelli, F. Lolli, A.M. Papini, and P. Rovero. Semi-Synthetic Strategies to Obtain Glucosylated MOG to Identify Antibodies as Biomarkers in Multiple Sclerosis Disease. In: Peptides for Youth: The Proceedings of the 20th American Peptide Symposium S. Del Valle, E. Escher, W.D. Lubell (Eds.), Springer (2009), pp. 327-328. ISBN: 978-0-387-73656-3.

F. Real-Fernández, A. Chamois-Colson, J. Bayardon, F. Nuti, E. Peroni, M.R. Moncelli, R. Meunier-Prest, S. Jugè, and A.M. Papini. Synthesis Of Organometallic Glycopeptides And Electrochemical Studies To Detect Autoantibodies In Multiple Sclerosis Patients´ Sera. In: Peptides for Youth: The Proceedings of the 20th American Peptide Symposium S. Del Valle, E. Escher, W.D. Lubell (Eds.), Springer (2009), pp. 435-436. ISBN: 978-0-387-73656-3.

S. Carganico, M.A. Bonache, M.C. Alcaro, M. Chelli, P. Rovero, M. Chorev, A. Lapolla, P. Traldi, and A.M. Papini. Synthetic strategies to Advanced Glycation End products peptides involved in diabetes. In: Peptides for Youth: The Proceedings of the 20th American Peptide Symposium S. Del Valle, E. Escher, W.D. Lubell (Eds.), Springer (2009), pp.  ISBN: 978-0-387-73656-3.

S. Pandey, E. Peroni, M.C. Alcaro, F. Rizzolo, M. Chelli, P. Rovero, F. Lolli, A.M. Papini. Mimicry Effect of the Neo-Epitope [Asn641(Glc)]FAN(635-655) with CSF114(Glc) Detecting Autoantibodies in Multiple Sclerosis. In: Peptides 2010, Proceedings of the 31st European Peptide Symposium. Michal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors). 2010 pp 4-5. ISBN 0-9715560-5-9.

F. Rizzolo, F. Nuti, S. Pandey, M. Chelli, P. Rovero, A.M. Papini. Microwave-Assisted Solid Phase Synthesis of [Asn641(Glc)]FAN(635-655): A New Case Study for Optimisation of Glycopeptide Synthesis. In: Peptides 2010, Proceedings of the 31st European Peptide Symposium. Michal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors). 2010 pp 186-187. ISBN 0-9715560-5-9.

S. Pandey, D. Lambardi, F. Real-Fernández, M.C. Alcaro, E. Peroni, M. Chelli, A.M. Papini, F. Lolli, P. Rovero. Recognition of Cytoskeletal Proteins Monoclonal IgGs by CSF114(Glc), the Synthetic Probe of Multiple Sclerosis. In: Peptides 2010, Proceedings of the 31st European Peptide Symposium. Michal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors). 2010 pp 290-291. ISBN 0-9715560-5-9.

F. Real-Fernández, I. Passalacqua, E. Peroni, F. Lolli, P. Rovero, A.M. Papini. Characterisation of the Minimal Epitope Detecting Autoantibodies in Multiple Sclerosis by Surface Plasmon Resonance. In: Peptides 2010, Proceedings of the 31st European Peptide Symposium. Michal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors). 2010 pp 498-499. ISBN 0-9715560-5-9.

F. Gori, B. Mulinacci, L. Massai, F. Lolli, A.M. Papini, P. Rovero. Antigenic Probes for Autoantibody Detection in Multiple Sclerosis: Synthetic Peptides versus Recombinant Proteins. In: Peptides 2010, Proceedings of the 31st European Peptide Symposium. Michal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors). 2010 pp 500-501. ISBN 0-9715560-5-9.

S. Pandey, E. Peroni, P. Rovero, F. Lolli, M. Chelli, A.M. D’Ursi, A.M. Papini. Rational Design and Optimization of the Newly Designed Glycopeptide Sequence to Develop the Diagnostic/Prognostic Assay for Multiple Sclerosis. In: Peptides 2010, Proceedings of the 31st European Peptide Symposium. Michal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors). 2010 pp 504-505. ISBN 0-9715560-5-9.

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