- Curriculum Vitae
Roberto Corradini-cv on 10/1/2021
Full Professor of Organic Chemistry, Department of Chemical Sciences, Life and Environmental Sustainability - University of Parma.
Date of Birth: 31-12-1963
Studies: Doctorate in Chemical Sciences, University of Parma, 1992, Degree (110/110 cum laude) in Chemistry, University of Parma, 1987.
Academic career: January 1, 2020 - today: Director of the Department of Chemical Sciences, Life and Environmental Sustainability - University of Parma. January 1, 2020 - today Member of the Academic Senate of the University of Parma. October 2018-today Full Professor of Organic Chemistry SSD CHIM / 06 University of Parma. 2000-2018 Associate Professor, University of Parma. 2013-National Scientific Qualification (ASN): qualification for full professor in 03 / C1-Organic Chemistry. 2007-today Member of the Teaching Board of the PhD in Chemical Sciences, University of Parma. 2017-2019 Coordinator of the PhD in Chemical Sciences; 2013-2017: Deputy Coordinator of the PhD in Chemical Sciences. 1996–2000 Researcher, University of Parma. 1994-1995 Post-doc fellow at the Department of Organic and Industrial Chemistry - University of Parma. 1991 Research period at the Institute de Biophysique- Museum National d’Histoire Naturelle Paris (with Prof. Claude Hèléne).
Awards: 2015 - Research Award "Organic Chemistry in its aspects of structural determination and molecular interactions" of the Organic Chemistry Division of the Italian Chemical Society. 1992 - “Chirality” Award of the Waters Company, Univ. Di Parma.
Hindex (ISI-WOS): 40 H index (SCOPUS): 41 (updated on 10/1/2021)
ISI publications (Core Collection): 177, of which articles in ISI journals: 151.
Book chapters: 19
Citations: 4381 (WOS, without self-citations: 3619); 4678 (SCOPUS)
N. International patents: 1 (extended to USA, Japan, Canada and EU). N. National patents: 1.
For comparison, the medians obtained from the ASN table of Ministerial Decree no.589 of 8/8/2018, for the competition sector 13 / C1 (Organic Chemistry), are shown, compared with the values for Roberto Corradini (RC), obtained by WOS on 10 / 1/2021.
Thresholds for ASN Jury members: articles last 10 years: 41 (RC: 59), citations last 15 years: 1277 (RC: 2011), Hindex last 15 years: 21 (RC: 27). Thresholds for Full professors: articles from the last 10 years: 27 (RC: 59), citations from the last 15 years: 816 (RC: 2011), Hindex last 15 years: 16 (RC: 27). Thresholds for Associate Professors: articles last 5 years: 13 (RC: 28), citations last 10 years: 329 (RC: 1132), Hindex last 10 years: 11 (RC: 20).
Responsibility for research projects: 2017-today: head of units at WP leader in the MSCA-RISE Oligo Nanomed project; 2015-2018. Head of the Parma Unit (linked third party) and WP leader in the H2020-ULTRAsensitive PLAsmonic devices for early CAncer Diagnosis (ULTRAPLACAD) project. 2011-2014 National Coordinator of a PRIN09-Molecular recognition of micro-RNA (miR) project by modified PNA: from structure to activity. 2020-today Head of the P-Teran project funded by the Emilia Romagna Region (Laboratory for entrepreneurship). 2018-2020-Local Project Manager Cystic Fibrosis Foundation ((CF-miRNA-THER). 2016-2017 Local Project Manager Cystic Fibrosis Foundation (MIRORNA-CF). 2012-2015. Local Project Manager Spinner (Emilia Romagna Region) PNA-NOVA ; 2012-2014: Local project manager TOPTHAL- FILAS-CR-2011-1054 Funded by the Lazio Region, in collaboration with IRBM (Pomezia); 2007-2009 Local manager for research activities in the European project EUROBIOTECH.
Research Interests. Bioorganic Chemistry: synthesis of molecules designed for the molecular recognition of species of biological interest. In particular, RC has carried out research in the following sectors in chronological order: 1) development of molecules able to discriminate enantiomers of amino acids, hydroxy acids and derivatives; 2) development of fluorescent sensors based on cyclodextrins for the detection of ions, organic molecules and for the discrimination of enantiomers; 3) identification and detection of toxins of food interest; 4) synthesis and structural properties of modified peptido-nucleic acids (PNA); 5) PNA synthesis for therapeutic applications by anti-gene and anti-miR strategy; 6) development of diagnostic systems and genosensors based on PNA; 7) conjugation of PNA and nucleic acids with nanostructured materials.
Teaching. 2000-04; Laboratory of Organic Chemistry 2, Degree in Chemistry, Faculty of Sciences, University of Parma. 2001-11; Course in Bioorganic Chemistry and Peptide Chemistry for the Degree Course in Biotechnology, Faculty of Sciences, University of Parma, 2004-10; Course in Organic Chemistry for the Degree Course in Biotechnology, Faculty of Sciences, University of Parma 2008-2014; Bioorganic Chemistry Course (module for the academic years 2009/10 and 2010/11) for the Master of Science in Molecular Biology, Faculty of Sciences, University of Parma 2009-10; Course in Organic Chemistry for the Degree Course in Mechanical Engineering, Faculty of Engineering, University of Parma 2010-today; Course in Organic Chemistry and Bioorganics for the Degree Course in Biotechnology, University of Parma. 2014-15. Course of Reaction Mechanisms for the Master of Science in Chemistry, Department of Chemistry, University of Parma. 2015-today Course of Organic Chemistry of Materials, for the Master's Degree in Chemistry, University of Parma (from 2017 1 module). 2017-2020 Course in Organic Chemistry for Biotechnology (2 module). Courses for PhD. Chirality and Chiral Discrimination (University of Parma, 2 editions: 3-15 July 2016, 6-23 July 2019).
Supervisor of eight PhD theses in Chemical Sciences at the University of Parma, one of which received a national award (CINMPIS). Supervisor of two PhD theses in Chemical Sciences in progress at the University of Parma. 2000-today: Thesis supervisor or co-supervisor (Five-year, Master's) in Chemistry (27), Food Science and Technology (10), Molecular Biology (2) and Industrial Biotechnology (1) at the University of Parma. External supervisor of a thesis in Biochemistry for the P.J. University Šafárik of Košice (Slovakia) in 2006 and a thesis in Chemistry at the University of Ghent (Belgium) in 2014. Supervisor or co-supervisor of a Bachelor's Thesis in Chemical Sciences and Technologies or Chemistry (17), Biotechnology (> 28), and Food Science and Technology (1) at the University of Parma.
Participation in PhD Jury: 1) University of Padua-PhD School in Molecular Sciences-Chemical Sciences (Italo-French Doctorate) 30/3/2009; 2) University of Parma, PhD in Chemical Sciences - 4/3/2010; 3) University of Ferrara –Doctorate in Biochemistry, Molecular Biology and Biotechnology 22/2 / 2011– 4) University of Naples Federico II PhD in Chemical Sciences 15/12 / 2011– 5) University of Pisa- PhD in Chemical Sciences-30- 31/1/20122) 6- University of Parma, PhD in Chemical Sciences - 20/3/2015 (Italian-French Commission), 7- University of Parma, PhD in Chemical Sciences (18/3/2016). 8- University of Parma, PhD in Chemical Sciences (09/3/2020). External referee for PhD thesis abroad: University of Pune (India) in 2008, University of Gent (Belgium) and Twente University (Netherlands) in 2016, ISIS Institute-University of Strasbourg (France) in 2017 (for the last two there was also participation in the final defense).
January 1, 2020 - today: Director of the Department of Chemical Sciences, Life and Environmental Sustainability - University of Parma. 2108-2019-Scientific Coordinator of the project for Departments of Excellence of the Department of Chemical Sciences, Life and Environmental Sustainability-University of Parma (Laboratory COMP_HUB). 2017-present. Delegate for Research Quality of the SCVSA Department. 2015-2017: delegate for research of the Department of Chemistry, University of Parma; 2013-2017. 2010-2014: Head of Scientific Degrees Plan (PLS) - Parma Chemistry Area; 2005-2017: member of the Area 103 Committee for the Research evaluation of the University of Parma. 2010-2012 Head of the Faculty of Science for services for the Disabled and for special weaknesses. 2013-Member of the Organizing Committee of the event "The Researchers' Night-The Sciences in Parma" (27 September 2013); 2011 -Membre of the Organizing Committee of the event "C’e’ Chimica tar noi (There is Chemistry between us)-In Parma" (https://sites.google.com/site/chimicafranoi/home) for the promotion of the role of Chemistry in society. (21-22 October 2011). 2009-2015: Responsible for orientation activities for the Degree Courses in the Chemistry area of the University of Parma. 2008-2019. Internship manager for the Biotechnology Degree Course.
International Symposia : 1) Chirality 2001- National Japanese Symposium on Chirality, Luglio 2001, Osaka, Giappone; 2) 19-Symposium on Chirality ISCD-19 at San Diego (U.S.A) Luglio 2007; 3) 6-10th International Symposium on Immunological, Chemical and Clinical Problems of Food Allergy”, Parma Maggio 2008; 4) VII Spanish Italian Symposium on Organic Chemistry (VII SISOC), Oviedo (Spagna) settembre 2008; 5) 21-Symposium on Chirality 2009-ISCD 21 (Breckenridge, Colorado, USA) Luglio 2009; 6) World Congress on Drug Discovery and Therapy (Boston, 3-6 giugno 2013); 7) COST Action TD1003 "Bio-inspired Nanotechnologies for Biosensing" meeting, 16/5/2013 (Sitges, Spain); 8) FEBS Workshop “Decoding non-coding RNA in development and cancer”, 12-16 ottobre, 2014 (Capri, Italy); 9) Biophotonics 2015, 3rd International Conference on Biophotonics, Firenze 20-22 Maggio, 2015. National Congresses: 1) Biotech.Org “Chimica organica e Biotecnologie: Sfide e Opportunità” Forte dei Marmi (LU) Maggio 2009; 2) XXXVI Convegno Nazionale della Divisione di Chimica Organica, Bologna, 13-17 Settembre 2015 (Award lecture) 3) SUPRAMOL 2017 13th Italian Conference on Supramolecular Chemistry, S. Margherita di Pula (Ca) 18-21/6/2017. In Companies: 1) DSM Research, Geleen, Olanda, 2003; 2) MERCK, IRBM Institute, Pomezia, 9/11/2007; 3) Sanofi-Aventis Chilly-Mazarin, Paris, France, 29/3/2010. Seminars in other Universities: 1) Università di Verona 18/6/2002; 2) Universitè Sacre Coeur di Namur (Belgio) 10/10/ 2012; 3) Università di Bologna 21/1/2013; 4) Université de Strasbourg-ISIS Institute (France) 11/6/2013; 5) Università della Svizzera Italiana di Lugano (CH), 8/11/2013; 6) University of Gent (Belgio) 27/6/2014; 7) University of Twente (Netherlands) 27/10/2016, Gent University (Belgium) 21/11/2019. Advanced shools/workshop: 1) XXVIII Summer School "A. Corbella", Giugno 2003, Gargnano, Italia; 2) PhD course in “Pharmaceutical Chemistry”- - Università di Milano, 26/5/2005; 3) “Young Researcher One Day Workshop on bio-nanoscience”- Laboratorio LATEMAR-Politecnico di Torino, 27/9/2006; 4) Workshop “Homeland Security Technologies” , Finmeccanica 26/10/2006; 5) Workshop “Metodi innovativi per il controllo e la tracciabilita’ di OGM ed alimenti contenti OGM”. ISPESL-Roma, 27/3/2007. 6) Workshop “Ricerca ed innovazione per la filiera olivicolo-olearia dei Paesi del Mediterraneo”, Fiera Agri – Levante Bari 19 /10/2007; 7) PhD course in “Pharmaceutical Chemistry”- Università di Milano, 20/6/2008; 8) International School in Nanoscience- Scuola Superiore di Catania, 25/7/2008; 9) International School in Nanoscience -Scuola Superiore di Catania, 25-26/6/2009; 10) International School in Nanoscience - Scuola Superiore di Catania, 25-26/5/2010, 11) HyNano - Summer School on Hybrid (bio)Nanostructures, Alghero (Italy), 3-7/9/2019.
Editorial activity: 1-2017-2018 Guest Editor of a special issue of the Molecules magazine (MDPI) dedicated to the Chemistry of NAPs; 2-2010-2015: Member of the Editorial Board of Chirality magazine (Wiley-VCH). 3-2012-2016 member of the Editorial Board and Acquisition Editor of the journal Artificial DNA, PNA & XNA (Landes Bioscience then Taylor & Francis). 4-Co-Editor of the book: ‘Detection of non amplified genomic DNA’ for the Springer Publishing House ("Soft and Biological Matter" Series, 2012). 5-Guest editor of a Special Issue (2/2012) of the journal Artificial DNA, PNA and XNA (Landes Bioscience), 2012 (vol3, n.2).
Referee and evaluation activities. Journals: Nature Communications, Journal of the American Chemical, Society, Chemistry-a European Journal, ChemBiochem, Organic Letters, Journal of Organic Chemistry, European Journal of Organic Chemistry, Organic and Biomolecular Chemistry, Journal of Physical Chemistry A, Langmuir, Journal of Inclusion Phenomena, Journal of Chromatography (A, B, Symposium Series), Material Science and Engineering C, Journal of Agricultural and Food Chemistry, Chirality, Dalton Transactions, Chemical Science, ACS Applied Materials & Interfaces, Biosensor and bioelectronics, Bioconjugate Chemistry, Future Microbiology, Proceedings of the National Academy of Sciences, India Section B: Biological Sciences, Biopolymers: Peptide Science, Chirality, Small, Scientific Reports, Molecules, Supramolecular Chemistry .
Institutions: Petroleum Research Fund (Washington, DC) .Czech Science Foundation (Czech Republic), State Secretariat for Education and Research - (Federal Republic of Switzerland), Austrian Science Fund (Austria), United Arab Emirates University (United Arab Emirates ), ANVUR (Italy), Italian Consortium of Biotechnology (CIB, Italy), European Commission (REA).
Membership. 2017-today Member of the Directive board of the Interdivisional Biotechnology Group of the Italian Chemical Society (SCI). Member of the SCI (Division of Organic Chemistry and Chemistry of Biological Systems and interdivisional group of Biotechnologies). Member of the American Chemical Society (Division of Organic Chemistry). Member of the National Institute of Biostructures and Biosystems (INBB. Italy). Member of the National Institute of Materials Science and Technology (INSTM).
National Research Collaborations in the last 5 years:
Prof. Roberto Gambari, Università di Ferrara, Prof. Sergio Ferrari UniMoRe, Prof. Giuseppe Spoto, Università di Catania, Prof. Emanuela Licandro, Università di Milano, Prof. Maria Minunni, Università di Firenze, Prof. Francesco Ricci, Università di Roma Tor Vergata, Dr. Michele Saviano, CNR Bari, Patrizio Giacomini, Istituto Regina Elena, Roma , Prof. Giulio Cabrini, Ospedale Universitario di Verona, Prof. Massimo Delledonne, Università di Verona, Dr. Mattia Asti, IRCCS-Reggio Emilia Ospedale Santa Maria Nuova.
International Research Collaborations in the last 5 years:
Peter E. Nielsen del Panum Institute, University of Copenhagen (Denmark); Luisa de Cola, dell’ Istituto ISIS, Università di Strasbugo; Wolfgang Knoll (Direttore) Austrian Institute of Technology, Vienna (Austria), Michael J Sailor, University of Californa San Diego, Nina Berova, Columbia University (New York, USA), Juriaan Huskens, University of Twente (Olanda), Annemieke Madder, Università di Ghent (Belgio), Stavros Pissadakis, Foundation for Research and Technology-Hellas (FORTH) (Grecia), Prof. Jiri Homola, Institute of Photonics and Electronics (IPE) Prague, Czech Republic.
Research activity - Brief narrative description
The research activity of Prof. Roberto Corradini has been devoted to the synthesis and study of molecular recognition systems of species of biological interest, and in particular to enantiomers of chiral substances, with the aim of designing molecules useful for diagnostic applications and pharmaceuticals and for the study of the role of chirality in molecular interactions. In this field, over the years he has carried out research in different phases centered on different topics: 1) at first he devoted himself to the enantiomeric recognition of amino acids and derivatives with chiral ligands; 2) from this research he developed skills for the realization of artificial receptors based on cyclodextrins; these receptors were then equipped with fluorescent groups to make fluorescent sensors for ions and neutral molecules, and in particular enantioselective sensors have been realized; 3) the recognition capabilities of cyclodextrin receptors also developed towards the complexation of food-type toxins, while providing support for the identification of toxins and metabolites with NMR techniques; 4) in the last fifteen years, the research has shifted towards the application of Supramolecular Chemistry to the recognition of nucleic acids acquiring an internationally recognized competence on the synthesis and modification of peptido-nucleic acids (PNA), with particular attention to stereochemistry and to the role of chirality; this study is currently conducted also with molecular modeling methods, in particular with molecular and metadinamic dynamics; 5) the competences acquired in this field have been used for the realization of systems of great interest from the application point of view, in particular in the development of new drugs, with innovative approaches such as the regulation of gene expression using anti-gene and anti-genetic approaches -miR, with great potential for therapeutic purposes. 6) At the same time, an activity was developed aimed at exploiting PNAs as advanced probes for DNA analysis, both towards biomedical applications (detection of DNA linked to pathological states), but also opening the field to applications in the food sector; this activity proved to be of great impact and also industrial interest, as evidenced by the participation in H2020 projects of industrial interest. The group has also had a pioneering role in biophotonics, with the creation of genosensors based on photonic crystal optical fibers 7) Some new applications have been developed exploiting the conjugation of PNA with nanostructured materials such as zeolites, metal-organic framework, and graphene oxide, for the realization of multifunctional systems. Research in this area is currently in progress and is being developed at the Department of Chemistry of the University of Parma, in the Laboratory called "Bioorganic Chemistry - Artificial Nucleic Acids" of which Roberto Corradini is the research leader and group leader.
Annex 1 shows the various research topics concerning the entire career in greater detail, with particular reference to those developed in the last 15 years.
Annex 2 contains a list of the doctoral theses of which Roberto Corradini was supervisor.
The complete list of publications is available separately.
Annex 1 - Detailed description of the research activity
(References to works specifically cited refer preferentially to the years 2006-2020)
The research activity of Prof. Roberto Corradini was dedicated to the synthesis and study of molecular recognition systems of species of biological interest, and in particular to the enantiomers of chiral substances, with the aim of designing molecules useful for diagnostic and pharmaceuticals and for the study of the role of chirality in molecular interactions. In this field, over the years he has carried out research in different stages focusing on different topics.
1) Recognition of enantiomers in chromatographic and electrophoretic methods. In this context, tetraamide receptors capable of binding via hydrogen bonds have been developed, derivatives of amino acids, which have been used as chiral stationary phases in gas chromatography, and complexes of chiral bis- or tetradentate ligands, which are used as additives to eluent in ligand exchange chromatography (LEC), for separating enantiomers of amino acids and other similar molecules. In an extension of this work metal complexes of cyclodextrins functionalized with chelating residues, in particular histamine and 2-aminomethylpyridine, were used as receptors for bifunctional molecules. The enantiomeric recognition mechanism proved to be a combination of ligand exchange and inclusion processes. Positively charged cyclodextrin-based receptors have also been used in capillary electrophoresis for the resolution of dansylated amino acid and aromatic acid enantiomers. These researches are recalled in contributions to the books: Chiral Separation Techniques - Wiley 2006, and D-Amino Acids, Nova Science, 2006,).
2) Chemo- and enantioselective fluorescent sensors based on cyclodextrins derivatized with groups containing the dansyl fluorophore, have been designed and synthesized. These molecules showed special properties due to the self-inclusion of the fluorophore in the cyclodextrin cavity, and were found to produce changes in fluorescence intensity by interaction with neutral molecules. The detection of copper (II) ions was obtained selectively, by exploiting the fluorescence quenching by this ion on a cyclodextrin containing dansyldiethylenetraimine. Later this model was implemented to allow the detection of chiral molecules. A series of fluorescent cyclodextrins, containing a thermo-bonding site have been designed to allow quenching with copper (II) ion; the copper complexes thus formed are able to function as enantioselective fluorescent sensors for unmodified amino acids. Using these sensors it was possible to realize a very fast parallel analysis system to measure the enantiomeric excess of amino acids and derivatives, by means of a multiwell fluorescence reader, as demonstrated by a work in collaboration with DSM-Geleen, The Netherlands (J Mater Chem 2005, 15, 2741-2746). Studies have been carried out on the mechanism by which these systems operate, which have made it possible to clarify both the detection process and the parameters that influence enantioselectivity (J Incl Phenom Macrocycl Chem 2007, 57, 625-630). The expertise acquired in this area was used in the drafting of an invited review on the topic of enantioselective fluorescent sensors (Topics in Current Chemistry 2011 ,. 300: 175–216).
3) Detection of toxins and their metabolites. Systems based on cyclodextrins have also been used to increase the fluorescence of contaminants of food interest, in particular mycotoxins, the detection of which is of great importance in food safety. In particular, fluorescence and NMR studies were performed to highlight the supramolecular interactions of some of these toxins (aflatoxins, ochratoxins and zearalenone) with cyclodextrins; the results have allowed to develop new chromatographic methods (Mycotoxin Res. 2008, 24, 14-18, World Mycotoxin J. 2008, 1, 397-406). A series of NMR studies have also been performed for the identification of metabolites of mycotoxins in collaboration with the group of R. Krska, (University of Natural Resources and Life Sciences, Vienna, Austria), using the classical approaches of the study of the chemistry of substances. natural organics (Food Addit Contam A 2009 26. 507-511; J. Agricolt. Food Chem 2011, 59, 9709–9714).
4) Synthesis and structural properties of chiral nucleic peptide acids (PNA). PNAs are oligonucleotide analogs with a polyamide skeleton consisting of N- (2-aminoethyl) glycine. These compounds are able to interact with great affinity and selectivity with complementary DNA RNA sequences. Roberto Corradini contributed to the realization of modified PNAs containing one or more stereogenic centers and rationalized the effects of stereochemistry on DNA binding properties and sequence selectivity (Chirality, 2007, 19, 269-294; Curr. Topics Med. Chem ., 2007, 7, 681-694). New peptide synthesis methods have been developed for the synthesis of modified PNAs and new chromatographic methods for the determination of the enantiomeric purity of monomers. In a fundamental work the structure of the duplex formed by a chiral PNA with its complementary DNA was determined (Proc. Nal Acad Sci USA, 2002, 100, 12021-12026), and the knowledge of the structural parameters allowed to rationalize the design and the synthesis of new modified PNA monomers (Tetrahedron Lett., 2011, 52, 300-304, Org. Lett. 2016, 18, 5452−5455, Organic Lett. 2021, In press). Structure-activity relationship studies were conducted by measuring the thermal stability of PNA: DNA adducts and by circular dichroism (CD). A systematic study of monomers containing all possible configurations in different positions of the PNA skeleton proved to be perfectly in line with the predictions based on this structure (Eur. J. Org. Chem. 2007, 5879–5885). The introduction of PNA monomers derived from amino acids allowed to confer typical properties of cellular and nuclear vehicular peptides (Eur. J. Org. Chem 2010 2441-2444) The expertise acquired in this sector was used in the recent drafting of a review by invitation on the topic of structural modification of PNAs and relevance in pharmaceutical applications (Curr Top Med Chem 2011, 11, 1535-1554) and a book chapter by invitation on the circular dichroism of PNAs and their derivatives (in "Comprehensive Chiroptical Spectroscopy, Wiley, 2012). More recently, the role of the presence of substituents on the PNA skeleton has been the subject of a modeling work, based on molecular dynamics and metadynamics, conducted in collaboration with Dr. Vincenzo Verdolino of the ETH Lugano Campus, (Sci Rep . 2017, 7, 42799).
Roberto Corradini has also proposed and coordinated the work of synthesis of modified nucleobases starting from uracil, which allow to realize modified PNAs also with residues that orient themselves along the major groove of the PNA: DNA duplex. A series of uracil derivatives have been produced for this purpose: these molecules have been shown to be biologically active in themselves as cell differentiation agents (J Med Chem 2009, 52, 87–94; Eur. J Pharmacol, 2011, 672, 30-37). Uracil-based dimeric nucleobases have been shown to be able to increase the selectivity and stability of PNA: DNA adducts and to promote self-assembly processes of PNA, being able to bind adenine with Watson-Crick and Hoogsteen hydrogen bonds. and provide additional stacking interactions (A. Accept, PhD Thesis, 2010, University of Parma). To achieve these modifications more effectively, PNA modification strategies at the nucleobase level were developed directly on the solid phase during peptide synthesis, using 5-azidomethyluracil as precursor (Artificial DNA, PNA & XNA 2012, 3, 53-62). This technique was used to create an efficient DNA detection system, selective for point mutations, based on PNA modified on the base with pyrene residues, highlighting an ability of these molecules to favor triple helix structures (Beilstein J. Org. Chem. 2014, 10, 1495-1503). Methodologies have therefore been developed to create polyfunctional PNAs, which lead to modifications both on the backbone and on the base, able to operate multiple processes (such as cell transport, recognition and detection of nucleic acids, catalysis) and to carry groups functional both within the major and minor sulcus of the PNA: DNA and PNA: RNA duplexes, and able to undergo a process of "induced fit" following complexation, as illustrated in the first published example (Org. 2016, 18, 5452−5455).
The introduction of reactive groups capable of modifying the structure of the target DNA is one of the most important objectives for biological applications. This goal was pursued by exploiting the collaboration with Prof. Annemieke Madder (University of Ghent), expert in cross-linking reactions mediated by furan residues. New PNAs containing furan residues both bound to the nuclebase and in place of it have been synthesized; the latter have proved capable of giving cross-linking reactions triggered by oxidizing agents (Chem Commun. 2016, 52, 6930-6933); better results were obtained by increasing the stability of the adducts obtained by using PNA with backbone modified in C5 with cationic residues (Molecules, 2017, 22, article n. 2010).
The PNA: PNA complexes are also excellent "intelligent" materials capable of producing self-assembling through programmable interactions based on the choice of sequences. In a work lasting several years in collaboration with Mark M. Green and Neville Kallenbach (New York University), the properties of duplex PNA: PNA have been studied, both as DNA models and as new nanostructured materials with predefined helicity (Macromolecules, 2010, 43, 2692-270; contribution to the book “DNA Nanotechnology: Methods and Protocols” Spinger 2011). In collaboration with Nina Berova (Columbia University, New York), porphyrin-PNA conjugates were made and the structures of PNA: PNA duplexes containing two porphyrins were studied (Chirality, 2015, 27, 864–874). Following the idea of programmability of PNA: PNA interactions and using microarray technology, a simple computer model based on PNA: PNA interactions was also created, capable of solving non-deterministic logic problems (Artificial DNA, PNA and XNA, 2011 , 2, 16-22). In collaboration with P.E. Nielsen (Panum Institute, Copenhagen), PNA: PNA complexes with modified monomers from the Parma group were also studied as prebiotic models of peptide synthesis systems (ACS Chem. Biol., 2014, 9, 2612-2620).
5) Synthesis of PNA for therapeutic applications by anti-gene and anti-miR strategy
The experience gained in the synthesis of PNA has been used in some studies aimed at rationally regulating the mechanisms related to gene expression at the transcription level. Some PNAs have been developed as potential drugs for the control of gene expression with anti-sense, anti-gene and anti-miR mechanisms. Roberto Corradini contributed to achieving these objectives in a work conducted in collaboration with A. Pession, (University of Bologna r Hospital S. Orsola of Bologna), coordinating the work of synthesis and study of the properties of antisense and anti-gene PNA designed to block an overexpressed gene in some pediatric cancers (MYCN), linked with poor disease prognosis. In particular, it has been shown that a suitably designed PNA is able to block gene transcription by means of a DNA "invasion" mechanism (Mol. Cancer Ther. 2005, 4, 779-786; Chirality, 2008, 20, 494-500 ). An international patent has been filed on this application (PCT / IB2004 / 001297 extended to USA, Canada, Japan and EU). More recently, the efficacy of the anti-gene approach has been demonstrated in vivo (on mouse models), and experimental tests have been produced which confirmed the anti-gene mechanism and the persistence of PNA in the serum of treated animals. The PNAs produced by the Parma group have been shown to inhibit the in vivo growth of rhabdomiosarcoma, with a sequence-specific mechanism and with efficacy that reaches complete remission and without toxic effects. (Clinical Cancer Res 2012, 18,796-807).
Research in this field has recently turned in particular to the modulation of gene expression using PNAs directed against microRNAs (miRs), double-stranded RNA segments that are able to recognize and deactivate sequences found on mRNA. In this context, Roberto Corradini was the coordinator of a national PRIN09 project. PNAs directed against miR210 and miR221 were able to cause changes in cell differentiation and proliferation, due to the lower bioavailability of the miRs themselves. Cellular studies were conducted in collaboration with R. Gambari of the University of Ferrara (ChemMedChem 2011, 6, 2192-2202, Biochem Pharm, 2011, 82, 1416-1429, Epigenomics, 2011, 3, 733–745, Int. J. Oncol. 2012,41, 2219-2127). In this application, PNAs modified with chiral residues (deriving from arginine) have proven to be particularly effective for good cellular uptake and anti-miR efficacy, showing to behave both in a peptide-like manner (as polyR) and as nucleic acids. , with greater bistability than a simple PNA-peptide conjugate (ChemBiochem 2012, 13, 1327 - 1337). Subsequently, thanks to the contribution of an AIRC project and a SPINNER project (Emilia Romagna region), the anti-miR technique is applied to the fight against glioblastoma, with encouraging data on the possibility of treating drug-resistant cells (J Neurooncol 2014, 118 : 19–28,. Int. J. Oncol. 2016, 48, 1029-1038, Int. J. Oncol., 2019, 55, 59-68, Nucleic Acid Therapeutics, 2020, 30, 164-174.). An interesting application of this strategy consists in increasing the production of the defective CFTR protein in the pathology of cystic fibrosis (Molecules, 2018, 23, 71), a study carried out during a pilot project and a research project funded by the Cystic Fibrosis Foundation. This research also led to the development of new PNA delivery systems based on cationic calixarenes (Scientific Reports, 2019, 9,3036).
Modified PNAs have also been used in collaboration with the group of M. Komiyama (University of Tokyo) for the invasion of DNA double helices (Nucleic Acid Res. 2008, 36, 1464-1471; ChemBioChem 2009, 10, 2607 - 2612 ), a phenomenon that has allowed the creation of artificial restriction systems (ARCUT) of greater specificity and efficacy, opening up good prospects in the creation of "gene repair" systems and cell therapy. A notable step forward, suggested by RC, was the use of a single PNA capable of carrying out DNA invasion, through the action of the previously studied NLS peptide (Org. Biomol. Chem., 2013, 11, 5233- 5238).6)
6) PNA for the realization of advanced diagnostic systems
Using appropriately designed PNAs, and in particular chiral PNAs, a series of techniques for the detection of DNA of both biomedical and food interest have been developed. Chiral PNAs have proved very useful in the detection of point mutations and single nucleotide polymorphisms (SNPs). PNA beacons (molecular beacons) containing a fluororphine and a quencher have been made using peptide synthesis techniques, and have been used in chromatographic systems (HPLC) for the highly selective detection of point mutations (Org. Biomol. Chem. 2008, 6, 1232-1237). Chiral PNAs with appropriate stereochemistry have proved to be particularly effective in these applications (Chirality. 2009, 21, 245-253). In this context, advanced techniques have also been developed, such as surface plasmon resonance (SPR), surface plasmon enhanced fluorescence spectroscopy (Biointerphases 2006, 1, 113-122, Biointerphases 2007, 2, 80-88), surface plasmon imaging (SPRi) (ChemBiochem 2008, 9, 2067-2070), microarray technology and microcontact printing (Langmuir 2011, 27, 1536-1542, Mol. BioSyst., 2011, 7, 1902-1907), photonic crystal fibers (IEEE J Sel Top Quant 2010, 16, 967-972, IEEE J Sel Top Quant, 2012, 18, 1176-1183) or more accessible methods such as HPLC (J Agric Food Chem 2007, 55, 2509-2516), CE (Electrophoresis 2005, 26, 4310 –4316), PCR (Anal Biochem, 2005, 344. 174-182), colorimetric (J. Biochem. Biophys. Methods 2007, 70, 735–741) and fluorimetric (Mol. BioSyst., 2011, 7, 1684– 1692).
In the biomedical field, modified PNAs have been used for the more specific detection of point mutations associated with the onset of genetic diseases such as cystic fibrosis, (J. Mol. Rec. 2004 17, 76-84; Electrophoresis 2005, 26, 4310–4316, J Biomed Opt 2013, 18, Article Number: 057004) and Alzheimer's disease (Mol. BioSyst., 2009, 5, 1323–1330). Studies are underway for the use of PNA conjugated with radioisotopes for the detection of miRNAs in vivo (Sci. Rep., 2019, 9.3376); for this research RC participates in a MAE project of great bilateral importance with the USA together with Dr. Asti of the IRCCS of Reggio Emilia, which foresees the collaboration with the group of Federica Pisaneschi, at the University of Texas - (MD Anderson Cancer Center of Houston, USA).
Since 2001, RC has proposed and conducted research on the use of PNA for the detection of DNA in foods as specific markers of the origin of raw materials. Advanced diagnostic techniques have therefore been used for the detection of specific DNA traits, in particular for the detection of genetically modified organisms (GMOs) and food allergens and for varietal recognition (summarized in the review Chem Socy Rev 2011, 40, 221 -232). A particularly ambitious goal was to establish the varietal origin of trace DNA extracted from olive oil, through the detection of cultivar-specific SNPs; this has recently been achieved using microarray and digital microfluidics technologies (Artificial DNA, PNA & XNA 2012, 3, 63-72, Anal. Bioanal. Chem., 2013, 405, 615-624). The most important result in this sector in recent years has been the development, in collaboration with G. Spoto of the University of Catania, of an ultra-sensitive system for the "PCR-free" detection of genomic DNA, using PNA probes in a SPRI system with gold nanoparticles, which allowed to obtain results similar to those of real-time PCR, but with greater sensitivity. The work was also the result of a collaboration with the NEOTRON company (Modena), a leader in the sector of DNA analysis in food at European level (Biosen. Bioelectron. 2010, 25, 2095–2100). The concept of "PCR-free" analysis made possible by the use of PNA and nanostructured materials was the subject of a book published by Springer of which Roberto Corradini is Editor by invitation, together with G. Spoto (Detection of Non-amplified Genomic DNA, Springer, 2012). The methodology developed is the basis of the ULTRAPLACAD project, funded under Horizon2020, aimed at applications in the field of early cancer diagnostics. In this project, RC coordinated a work-package dedicated to the synthesis of the probes and the modification of surfaces. A recent work reports the success in the development of an ultrasensitive detection system for point mutations of the KRAS gene, applied to clinical samples in the 'Liquid Biopsy' mode, which has shown the effectiveness of detection by PNA probes (Biosen. Bioelectron , 2020, 170, 112648). Some works in collaboration with the group of J. Huskens (Twente University) have been dedicated to the study of the deposition of PNA on surfaces for sensory purposes (Langmuir, 2018, 34, 11395–11404, Bioconj. Chem. 2018, 29, 4110- 4118, ACS Appl. Pol. Mater. 2019, 1, 3165-3173.
A similar approach has also been achieved with the aid of photonic crystal optical fibers (PCF) (J. Lightwave Technol. 2016, DOI: 10.1109 / JLT.2016.2607024), with very positive results and the realization of the first genosensor based on PCF capable of directly detecting non-amplified DNA extracted from real samples (Biosens. Bioelectron 2015, 63, 248–254).
Still exploiting the performance of PNAs in the sensor field, but using an amperometric detection mediated by alkaline phosphatase, a method was developed in collaboration with Marco Giannetto of the University of Parma. (Biosensors and Bioelectronics, 2019, 129, 7-14; Sensors, 2019, 19, art.588).
7) Conjugation of PNA and nucleic acids with nanostructured materials
The recent collaboration of the RC group with Luisa de Cola (University of Strasbourg) goes in the direction of applying the knowledge acquired in the field of nucleic acids to the realization of multifunctional systems, based on inorganic nanostructures, able to combine the recognition properties of DNA and RNA with the ability to carry small molecules. This approach makes it possible to combine different types of therapy in a single treatment, such as a treatment with an anti-miR drug and at the same time with a small molecule, in addition to the simultaneous detection of therapeutic events (release, localization, etc.), in a "theranostic" approach. This was accomplished by functionalization of nanozeolites or mesoporous silica nanoparticles. In a first work, L-nanozeolites were used to carry DNA molecules and dyes (taken as a model of small molecule drugs, studying their cell fate (Chem. Eur. J., 2014, 20: 10900 - 10904). Then the same technique was used to deliver PNA into cells, covalently binding them to the support of zeolites (Adv. Healthcare Mater. 2014, 1812-1817). The simultaneous delivery of anti-miR221 PNA and an anticancer drug (temozolomide), made by the use of mesoporous silica nanoparticles has led to an increase in the ability to induce apoptosis in drug-resistant cells (Small, 2015, 11: 5687-5695.). The research group has also contributed to the development of proteins based on silica nanocapsules degradable in a reduced environment (Angew Chem. Int. Ed 2016, 55, 3323-7). Studies have also been carried out in parallel on the use of PNA in combination with other nanostructured materials, in particular and metal-organic framework (MOF) (Chem. Eur. J. 2017, 10.1002 / chem.201605803) and graphene oxide. This type of research is the subject of a European project MSCA-RISE Oligo Nanomed, coordinated by Luisa de Cola, of which RC is the local manager. In this project we intend to use different nanostructured materials for the programmed release of molecules of therapeutic interest. In this context RC spent a research period of 1 month (August 2018) at the University of Californa, San Diego in the laboratory of Michael J. Sailor, for the development of materials based on porous silicon loaded with PNA, the results of these studies are reported in a PhD thesis and in an article under preparation.
Attachment 2-List of PhD theses in Chemical Sciences followed as supervisor
1- Andrea Faccini: Modified Peptide Nucleic Acids (PNAs) for biomedical and biotechnological applications: synthesis and properties University of Parma (XVIII Ciclo 2003–2005).
2- Filbert Totsingan: Synthesis and Applications of PNA and Modified PNA in Nanobiotechnology-University of Parma (XX Ciclo 2005-2007)
3- Alessandro Accept: Molecular Engineering of PNA using Modified Uracil Derivatives and Porphyrins-University of Parma (XXII Ciclo 2007 - 2009)
4- Alex Manicardi: Modified peptide nucleic acids (PNAs) for nucleic acids detection and anti-miR activity University of Parma (XXIV cycle 2009 - 2011). (CINMPIS Prize for best PhD thesis in 2012).
5- Alessandro Bertucci: Hybrid organic-inorganic interfaces for biomedical applications University of Parma (XVII cycle 2012-2014) and University of Strasbourg. Thesis in co-tutorship with Prof. Luisa de Cola (ISIS Institute, University of Strasbourg).
6- Massimiliano Donato Verona: Modified PNA design and synthesis: a novel approach using Molecular Dynamics and Metadynamics (XVIII cycle 2013-2015).
7- Andrea Rozzi: Advanced PNA-based sensor systems (XXXI cycle 2015-2018)
PhD thesis in progress:
8- Martina Neri. Peptide Nucleic Acid (PNAs) and Modified PNAs-based strategies for Advanced Diagnostic and Therapeutic applications (XXXIII cycle, 2017-2019, under evaluation)
9- Federica Curti: Tentative title: Biophotonics and bioelectronics applications of nucleic acids and PNA (XXXIV cycle, 2018-2020)
10- Sabrina Capodaglio: Tentative title: PNA-based 'smart' nanostructured materials.
Anno accademico di erogazione: 2021/2022
Anno accademico di erogazione: 2020/2021
Anno accademico di erogazione: 2019/2020
Anno accademico di erogazione: 2018/2019
Anno accademico di erogazione: 2017/2018
Anno accademico di erogazione: 2016/2017
Anno accademico di erogazione: 2015/2016
Anno accademico di erogazione: 2014/2015
- First cycle degree (DM 270) BIOTECHNOLOGY A.Y. 2021/2022
- First cycle degree (DM 270) BIOTECHNOLOGY A.Y. 2020/2021
- First cycle degree (DM 270) BIOTECHNOLOGY A.Y. 2019/2020
- First cycle degree (DM 270) BIOTECHNOLOGY A.Y. 2018/2019
- First cycle degree (DM 270) Biotechnology A.Y. 2017/2018
- First cycle degree (DM 270) Biotechnology A.Y. 2016/2017
- First cycle degree (DM 270) Biotechnology A.Y. 2015/2016
- First cycle degree (DM 270) Biotechnology A.Y. 2014/2015
- First cycle degree (DM 270) Biotechnology A.Y. 2013/2014
- First cycle degree (DM 270) BIOTECHNOLOGY A.Y. 2021/2022
- First cycle degree (DM 270) BIOTECHNOLOGY A.Y. 2020/2021
- SCIENZE CHIMICHE A.Y. 2020/2021
- First cycle degree (DM 270) BIOTECHNOLOGY A.Y. 2019/2020
- First cycle degree (DM 270) BIOTECHNOLOGY A.Y. 2018/2019
- First cycle degree (DM 270) Biotechnology A.Y. 2017/2018
- First cycle degree (DM 270) Biotechnology A.Y. 2016/2017
- First cycle degree (DM 270) Biotechnology A.Y. 2015/2016
Year: 2021Author/s: VOLPI, STEFANO, CANCELLI, UMBERTO, NERI, MARTINA, CORRADINI, Roberto
Year: 2021Author/s: CASNATI, Alessandro, CORRADINI, Roberto, SANSONE, Francesco
Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () geneYear: 2021Author/s: MANICARDI, Alex, CORRADINI, Roberto
A peptide-nucleic acid targeting miR-335-5p enhances expression of cystic fibrosis transmembrane conductance regulator (CFTR) gene with the possible involvement of the CFTR scaffolding protein NHERF1Year: 2021Author/s: MANICARDI, Alex, CORRADINI, Roberto
PNA-functionalized magnetic microbeads as substrates for enzyme-labelled voltammetric genoassay for DNA sensing applied to identification of GMO in foodYear: 2021Author/s: FORTUNATI, SIMONE, GIANNETTO, Marco, ROZZI, ANDREA, CORRADINI, Roberto, CARERI, Maria