Anna Maria Papini
Professor, University of Florence
Aberrantly Modified Conformational Peptide Epitopes, Specific for Antibodies Biomarkers of Immune-Mediated Diseases, Can Be Reminiscent of an Early Infection. The Chicken or Egg Dilemma?
Autoimmune diseases affecting an increasing number of individuals throughout the world, represent a large and diverse group of disorders categorized by tissue injury or pathology. Thus, characterisation of reliable biomarkers is necessary not only for an early diagnosis but also for monitoring disease activity. Growing evidences indicate that aberrant post-translational (PTMs) modifications (i.e., acetylation, lipidation, citrullination, phosphorylation, glycosylation, glycation, etc.) may play a fundamental role in triggering specific antibody response to aberrantly modified native antigens in immune compromised diseases. We have been developing since years, structure-based designed N-glucosylated peptides, characterized by β-turn structures, as Synthetic Antigenic Probes (SAPs) accurately measuring in sera of statistically significant patient populations of neuroinflammatory diseases, i.e. Multiple Sclerosis and Rett Syndrome, high affinity antibodies as biomarkers of disease activity. This “chemical reverse approach” allowed to identify a cross-reactive hyperglucosylated bacterial adhesin protein, i.e., non-typeable Haemophilus influenzae that is leading to discover a possible early infection . Therefore, a series of peptide scaffolds modified with different aberrant PTMs, were designed, developed, and selected to recognise specific antibodies in coeliac disease , primary biliary cirrhosis , T1 diabetes , rheumatoid arthritis . On the other hand we and others demonstrated that glycoreplica peptides could mimic the carbohydrate epitope of human natural killer cell-1, HNK-1, that is considered the antigenic determinant of myelin-associated glycoprotein and the target of clinically relevant autoantibodies in autoimmune neurological disorders such as IgM monoclonal gammopathy and demyelinating polyneuropathy [6,7]. Therefore, the collection of these SAPs have been proposed to develop multiple diagnostic/prognostic immunoassays with a theranostic value. Last but not least, the SAPs can be fundamental tools to characterise cross-reactions with bacterial and/or viral infection-mediating enzyme activity involved in aberrant modifications of native antigens and triggering antibodies, as early causative agents of immune-dysregulation.
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A.M. Papini is Professor of Bioorganic Chemistry. She is coordinator of the Research Unit of Peptide and Protein Chemistry and Biology at the University of Florence. After completing an International PhD in 1990, under the supervision of Prof. Luis Moroder of the Max Planck Institut fuer Biochemie, in 1991 she founded the first Laboratory of Peptide Synthesis starting peptide-based translational research at the Biomedical & Technological Pole of the University of Florence (Italy). She has been Laureate of the “Chaire d’Excellence” 2009-2014 of the French “Agence Nationale de la Recherche” (unique for chemistry out of 16) to start in 2013 the platform PeptLab@UCP introducing for the first time peptide chemistry at the Université Paris-Seine (France) that since 2019 has a large scale KgLab peptide facility funded by the Region Ile de France. Since 2014 she has been appointed coordinator of the Interdepartmental Laboratory of Peptide & Protein Chemistry & Biology (www.peptlab.eu) associating the Departments of Chemistry, Neurosciences & Pharmaceutical Sciences of the University of Florence in Italy and PeptLab@UCP in France. In 2008 she obtained the Leonidas Zervas Award of the European Peptide Society and the 1st Dimitrios Theodoropoulos Memorial Award of the Hellenic Peptide Society. In 2019 she has been awarded with the Rita Levi Montalcini Prize for the binational cooperation between Italy and Israel for a research project aimed to characterise glycopeptide and glycoprotein antigens to investigate cross-reactions between immune-mediated diseases and infections. For the period 2011-2020, she has been nominated member of the Executive Committee of the European Peptide Society acting as treasurer and for the period 2019-2025 she has been elected councilor of the American Peptide Society. In 2015 she was one of the founders of the Italian Peptide Society and since 2017 she has been elected chief scientific officer in the executive committee. Since 2013 she is delegate of the International Affairs and Erasmus Program of the School of Sciences of the University of Florence supporting students interested in international education pathways. She was chair with Phil E. Dawson of the 2016 Gordon Research Conference “Crossing Barriers by Peptide Science for Health and Wellness” and she has been nominated Chair of the next 14th International Peptide Symposium/37th European Peptide Symposium that will organsie with Prof. Paolo Rovero in Florence (Italy) on August 28-September 3, 2022. She is cofounder of the first spin-off of the University of Florence EspiKem Srl, launched in 2003, of the start-up Toscana Biomarkers Srl (2007-2014), whose mission was R&D of peptide-based diagnostics of autoimmune diseases, licensing patents to diagnostic companies. For her activity in technology transfer she got in 2009 the Frost & Sullivan Excellence in Research Award in the European autoimmune disease diagnostics market & the Vespucci Award of the Regione Toscana for the perspectives of development of the company aimed to research and production of innovative diagnostic methodologies for autoimmune diseases. Moreover since 2017 she founded and acts as scientific coordinator of PeptFarm joining PeptLab of the University of Florence and Fabbrica Italiana Sintetici, F.I.S. Italy in the new Facility MoD&LS (funded by EU funds of the Region Toscana) to develop large-scale synthesis of peptide-drugs and she has recently founded Apotech that will obtain the status of spinoff of the University of Florence in the next months to develop cosmeceutical active peptides. She is coauthor of 258 peer-reviewed articles: 150 articles in peer reviewed scientific journals and 108 articles in peer reviewed books. She is coauthor of 11 filed patents. She has been invited to present 120 lectures in International Symposia, Universities and Research Centers. 53 oral & 245 poster communications were selected for presentations in international symposia. Moreover she was invited to present 10 lectures aimed to technology transfer in the global space of R&D (2 in extra-European countries and 8 in Europe). Since starting her independent career, she has trained 30 PhD and 73 undergraduate students (50 Masters and 23 Bachelors), 15 post-doctoral fellows and 11 research assistants in the field of peptide and protein chemistry and immunology focused on the characterisation of aberrant post-translational modifications in biomarkers of disease activity, structure-activity relationship studies, metabolic stabilization by exotic side-chain to side-chain cyclization. Some of her PhD students obtained important recognitions such as the 2016 Louis Forest « Prix de la Chancellerie des Universités de Paris, Honorable Mention of the 2005 Bert Schram Price from APS, 1999 Bruce W. Erickson Award.