Laura Cipolla

Current scientific interests focus on ● design and synthesis of several biologically active compounds, in particular carbohydrates and their structural analogues, and biologically relevant peptides and their mimetics ● Enzymes inhibitors of enzymes involved in relevant biological processes ● Development of innovative smart biomaterials  based on inorganic, organic or composite matrices. ● NMR studies for the elucidation of key details of ligand/receptor interactions ● Elucidation of molecular mechanism of key enzymes involved in physiological or pathological states

TRAINING AND RESEARCH EXPERIENCE Laura Cipolla’s research experience dates back to 1992 when she begun her experimental work on the synthesis of iminosugars as glycosidase inhibitors in Prof. Russo and Prof. Nicotra research group at Milano University. Between 1993 and 1996 she continued working in this research group as PhD student, gaining expertise in carbohydrate chemistry, especially in the synthesis of their analogues as potential inhibitors of carbohydrate processing enzymes, such as glycosidases and glycosyltransferases. In 1997 she moved to the Carlsberg Research Laboratory, Chemical Department, Copenhagen, as post-doc fellow, where she extended her know-how on the synthesis of peptides, and glycoconjugates, such as glycopeptides, neoglycopeptides and glycolipids. The first of October 1999 she joined the Department of Biotechnology and Biosciences of Milano-Bicocca University where she actually has a permanent position as Associate Professor in Organic Chemistry. Till nowadays Cipolla’s research experience has been focused on the synthesis of carbohydrates, their conjugates and their analogues, due to the great biological relevance of this class of biomolecules. Great expertise has been gained in the following topics: ● Synthesis of iminosugars and their evaluation as glycosidase inhibitors ● Synthesis of different C-glycosidic analogues of biologically relevant monosaccharides, such as phosphonate analogues of glycosyl phosphates as potential inhibitors of glycosyltransferases, C-glycosidic analogues of glyceroglycolipids, C-glycosidic analogues of 2-amino-2-deoxy-sugars. ● Synthesis and biological activity of glycopeptides and neoglycopeptides by solid phase chemistry as potential antitumor vaccines ● Studies on the synthesis of sugar amino acids as conformationally constrained scaffolds ● Studies on the use of recombinant biocatalysts for regioselective modification of carbohydrates ● Studies on the synthesis and biological activity of carbohydrate-based inositol analogues, as potential kinase inhibitors ● Studies on the synthesis of glycosyl phosphoramidates as analogues of glycosyl phosphates ● Studies on the synthesis and NMR characterisation of key enzymes involved in the biosynthesis of LPS ● Studies on the synthesis of novel proline mimetics, and their use as building blocks in the synthesis of neopeptides, benzodiazepines and GABA analogues ● Biofunctionalisation of inorganic materials for articular bio-prostheses development

Organic chemistry

Synthesis and Biological activity of PKB/Akt inhibitors

Protein kinases comprise a large family of enzymes that catalyse the transfer of the terminal phosphate group from ATP (adenosine triphosphate) to protein substrates, specifically to the hydroxyl group of serine or threonine (Ser/Thr kinases) or tyrosine (Tyr kinases). The serine/threonine protein kinase B (PKB), also known as Akt, phosphorylates diverse protein substrates to promote cell growth and survival, and to mediate the effects of insulin. Many lines of evidence demonstrate that Akt is a critical player in the development, growth, and therapeutic resistance of cancers. Akt can be activated in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner: PI3-K phosphorylates the 3-position of phosphatidylinositols to give rise to three signaling phospholipids (PI(3)P’s). Binding of the pleckstrin homology (PH) domain of Akt to membrane PI(3)P’s causes a conformational change in the molecule and its translocation to the plasma membrane; finally, phosphorylation of Thr 308 of the activation loop in the kinase domain. A valuable approach to selective and Akt-specific inhibitors is the development of substrate-competitive inhibitors: since the substrate-binding domain is less conserved than the ATP fold, they should be more specific then ATP mimetics.

A novel class of phosphatidylinositol (PI) analogues as substrate-competitive inhibitors selective for Akt, based on D-glucose as scaffold mimicking the inositol ring is under investigation.

Collaboration Prof. L. De Gioia (this Department), Prof. F. Granucci (this Department), and Prof. A. Zaza (this Department).

Synthesis and Biological activity of nojirimycin derived iminosugars

Polyhydroxylated nitrogen heterocycles, usually referred to as iminosugars, are known for their inhibitory activity toward carbohydrate-processing enzymes, suggesting their use in a wide range of potential therapeutic applications, such as treatment of diverse viral infections, such as human immunodeficiency virus (HIV), human hepatitis B virus (HBV), human hepatitis C (HCV), bovine viral diarrhea virus (BVDV), Japanese encephalitis virus (JEV) and dengue virus, as well as cancer, diabetes, tuberculosis, malaria and lysosomal storage diseases. Novel nojirimycin-derived bicyclic structures, containing cyclic carbamate, urea and guanidine moieties have been synthesised starting from suitably protected a-C-vinylnojirimycin and a-C-allylnojirimycin respectively, and their activity against different glycosidases tested. Biological activity of these iminosugars against bacterial toxins is currently under investigation.

Collaboration Prof. Klaus Aktories at the Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-Universität,Freiburg] .

Synthesis and Biological activity of conformationally constrained 1,4-benzodiazepin-2,5-diones and GABA analogues

1,4-Benzodiazepine (1,4-BDZ) derivatives are extensively investigated owing to their vast array of biological activities, and in recent times their structure has been widely used as a “molecular scaffold”.Recently, the design and synthesis of new chimeric scaffolds that are hybrids of benzodiazepines with sugars, wherein the latent hydroxyl groups of the carbohydrate moiety permit diverse, controlled derivatization at different sites have been proposed. In addition, great efforts have been devoted to the synthesis of conformationally constrained benzodiazepine derivatives, since conformational changes in the benzodiazepine ring system have an effect on binding affinities to the receptor complex.

Synthesis and preliminary biological evaluation as GABAA receptor ligands of novel 1,4-benzodiazepine-2,5-diones as chimeric scaffolds, containing both a monosaccharide and a proline moiety and GABA analogues is due course. The free hydroxyl groups on the sugar increase water solubility, while parent compounds have a low water solubility, and offer the possibility of further functionalisation for biological activity tuning. The sugar scaffold has been used to build the proline moiety.

Collaboration Prof. G. Giagnoni and. Dr. B. Costa (this Department).

Antibacterial drug development inhibiting outer membrane biogenesis of gram-negative bacteria

Despite important advances made in the last century, infectious diseases caused by pathogenic microrganisms still are a major threat to human health. Thus, the necessity to develop new weapons against pathogenic bacteria is widely recognized as a major challenge for modern biomedical research. Protein targets involved in the outer membrane biogenesis of gram-negative bacteria are being exploited for the design and synthesis of novel inhibitors.

Collaboration Prof. A. Polissi, Prof. L. De Gioia (this Department) Prof. G. Deho’ and Prof. M. Bolognesi at the Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano Dr. P. Mauri at the Istituto di Tecnologie Biomediche-CNR, Milano Prof. A. Molinaro, University of Naples

NMR studies of receptor/ligand interactions

NMR determination of SAR of PKB/Akt PH-domain and glucose-based inhibitors

Epitope mapping and NMR binding studies are currently being performed for glucose-based Akt inhibitors, in order to elucidate fundamental functional groups for interaction with the PH-domain of the target protein.

 Biocatalysis in organic chemistry 

 Studies on site-directed lipase mutants on regioselective acylation of monosaccharides.

Lipases (triacylglycerol ester hydrolases, EC 3.1.1.3) are ubiquitous enzymes that catalyse the hydrolysis of fats and oils. They are the most widely used enzymes in synthetic organic chemistry, as catalyst of the chemo-, regio-, and/or stereoselective hydrolysis of carboxylic acid esters or of the reverse reaction in organic solvents. Recently, genetic engineering approaches have become powerful tools to improve of enzyme performance, in general. Mutants F344V and F345V of Candida rugosa lipase1 (CRL1) were tested in acylation reactions of monosaccharide derivatives in order to study the regioselectivity, and the substrate specificity of lipase variants towards unnatural substrates, such as carbohydrates.

Collaboration Prof. M. Lotti (this Department)

Studies on thermophilic Esterases belonging to the HSL family EST2

Esterase 2 (EST2) from the thermophilic eubacterium Alicyclobacillus acidocaldarius is a thermostable serine hydrolase belonging to the HSL family of the esterase/lipase superfamily1–3 characterised by the a/b hydrolase fold. Members of this family are ubiquitous and comprise true lipases and amidases other than carboxylesterases and are still poorly characterised. EST2 has been tested in deacylation reactions of selected peracetylated monosaccharides.

Collaboration Dr. Giuseppe Manco, Institute of Protein Biochemistry, CNR, Via P. Castellino 111, 80131 Napoli, Italy

Development of novel synthetic methodologies.

Microwaves technique for easy access to glycosyl phosphorothioates

Glycosyl phosphonate and thiophosphate analogues of naturally occurring phosphates have found a wide range of applications as regulators, activators or inhibitors of carbohydrate-processing enzymessince they are isosteric and non-hydrolyzable analogues of phosphate esters.  A simple, efficient and general method for the synthesis of glycosyl phosphorothioate through a one-pot reaction of glycosyl bromide with diethyl phosphite, ammonium acetate and sulphur in the presence of alumina under solvent-free conditions, using microwave irradiation has been developed.

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Team composition The organic chemistry group of Laura Cipolla at the dept. of Biotechnology and Biosciences, University of Milano-Bicocca is composed by Prof. Laura Cipolla (Lab Head, Associate professor) and 6 experienced fellows: Dr. Francesca Taraballi (post-doc), Dr. Luca Gabrielli (PhD student in chemistry) Dr. Laura Russo (Post-doc), Dr. Davide Bini (experienced fellow), Dr. Alice Capitoli (postgraduated fellow), Dr. Cristina Lupo (post-graduated fellow) and 5 undergraduated students in Chemistry and Industrial Biotechnologies.

UNIMB, Team expertises. The scientific background of the research group focuses in general on the synthesis of bio-active molecules, and an extended knowledge on bioorganic chemistry has been acquired. In particular, great experience has been gained in carbohydrate chemistry, synthesis of their analogues as potential enzyme inhibitors and in the synthesis of other biologically relevant molecules, such as peptides and peptidomimetics. More recently, the research group extended and applied its expertises on biofunctionalisation of bio- and nano-materials, useful for a wide range of applications, such as theragnostic and tissue engineering; the group has experience in several chemical methodologies for biofunctionalisation, including chemoselective strategies, and can deal with different kind of biomaterials (organic, inorganic, polymeric, etc.).

UNIMIB, Team facilities The UNIMIB Unit will be located at Department of Biotechnology and Biosciences at the University of Milano-Bicocca. The Department has research laboratories over more than 4000 m2 with a variety of innovative and up-to-date instrumentations and facilities, including confocal microscopy, cell-sorting, Plasmon Resonance, Gene-chip, NMR spectroscopy equipped with cryoprobe and HR-MAS, mass spectrometry, bioinformatics facilities based on up-to-date instruments, Stabulary, a PL2 level laboratory and a Biotecnicum, for GLP production. Expertise at the Department are multidisciplinary, with many research collaborations both national and international, and with factories, mainly pharmaceutical. Laboratory Facilities in the Organic Chemistry lab: MALDI Kompact II-kratos analytical equipped with N2 laser, Time Of Flight Mass Spectrometry (TOF-MS); NMR Varian 400 MHz MERCURY; NMR Brucker 600 MHz cryoprobe/High Resolution Magic Angle Spinning; HPLC Waters equipped with both UV 486 detectors, 515 pumps, possibility of simultaneously working at two wavelengths. HPLC Jasco equipped with both UV 2075 plus detectors, PU-2080 pumps, Hercule Lite interface. Freeze-dryer Christ, Alpha1-2 LD, Krüss-Optronic P3002 polarimeter, 2 Rotary Vacuum pump Vacubrand, 4 Heidolph rotary evaporators, melting point apparatus. Core Facilities and Services: Affymetrix GeneChip Technology to monitor genome wide gene expression and integrated data analysis; Biacore system ; Real Time PCR machine; QSTAR Elite and QTRAP mass spectrometers by Applied Biosystems for MS, tandem MS/MS, LC/MS/MS, equipped with ESI. FT-IR coupled to UMA 500 infrared microscope equipped with a nitrogen cooled MCT detector to a FTS 40A spectrometer (Digilab-USA), Automated Microwave Peptide Synthesizer (Liberty-CEM), confocal microscope, several optical spectroscopies instruments for absorption, reflection, photoluminescence and ellipsometry, micro-Raman scattering, refractive index.

Current fundings:

CARIPLO FOUNDATION: project 2008-3175 “Development of NMR techniques for tissue Engineering studies” (PI: Prof. J. Jimenez Barbero, synthetic chemistry unic coordinator Prof. Francesco Nicotra and Prof. Laura Cipolla)

CARIPLO FOUNDATION: project 2010-0378 (1/6/2011-31/5/2013): “Nanostructured biomaterial functionalization for treatment of articular cartilage defects (PI: Prof. Laura Cipolla)

CARIPLO FOUNDATION: project 2010-0653 (1/6/2011-31/5/2011): “Outer membrane biogenesis in Gram negative bacteria as a target for innovative antibacterial drugs (PI: Dr. Paola Sperandeo, organic chemistry unit coordinator Prof. Laura Cipolla)

CARIPLO FOUNDATION: project 2011-0270 (1/3/2012-28/2/2015): Sintesi di una macromolecola brush-like con architettura e proprietà meccaniche biomimetiche ottimizzate (PI: Dr. Simone Vesentini, organic chemistry unit coordinator Prof. Laura Cipolla)

CARIPLO FOUNDATION: project 2011-0490 (1/3/2012-28/2/2014): Targeting pro-survival features of tumor cells by novel inhibitors of the AKT kinase (PI: Prof.Diego Colombo, organic chemistry unit coordinator Prof. laura Cipolla)

FINLOMBARDA-REGIONE LOMBARDIA-Fondo per la promozione di Accordi Istituzionali-2009 (15/6/2010-15/12/2011): project “Rational Drug Design to target outer membrane biogenesis of Gram-negative pathogenic bacteria (PI: Prof. Alessandra Polissi, organic chemistry unit coordinator Prof. Laura Cipolla)

REGIONE LOMBARDIA “Fondo Per La Promozione di Accordi Istituzionali” project NEDD 14546/2010 “Network Enabled Drug Design” (1/4/2011-31/3/2013). (PI: Prof. F. Nicotra, Phase Coordinator Prof. Laura Cipolla)

Synthesis and Biological activity of PKB/Akt inhibitors

Protein kinases comprise a large family of enzymes that catalyse the transfer of the terminal phosphate group from ATP (adenosine triphosphate) to protein substrates, specifically to the hydroxyl group of serine or threonine (Ser/Thr kinases) or tyrosine (Tyr kinases). The serine/threonine protein kinase B (PKB), also known as Akt, phosphorylates diverse protein substrates to promote cell growth and survival, and to mediate the effects of insulin. Many lines of evidence demonstrate that Akt is a critical player in the development, growth, and therapeutic resistance of cancers. Akt can be activated in a phosphatidylinositol 3-kinase (PI3-K)-dependent manner: PI3-K phosphorylates the 3-position of phosphatidylinositols to give rise to three signaling phospholipids (PI(3)P’s). Binding of the pleckstrin homology (PH) domain of Akt to membrane PI(3)P’s causes a conformational change in the molecule and its translocation to the plasma membrane; finally, phosphorylation of Thr 308 of the activation loop in the kinase domain. A valuable approach to selective and Akt-specific inhibitors is the development of substrate-competitive inhibitors: since the substrate-binding domain is less conserved than the ATP fold, they should be more specific then ATP mimetics. A novel class of phosphatidylinositol (PI) analogues as substrate-competitive inhibitors selective for Akt, based on D-glucose as scaffold mimicking the inositol ring is under investigation.

Collaboration

Prof. L. De Gioia (this Department), Prof. F. Granucci [LC1] (this Department), and Prof. A. Zaza (this Department).

Synthesis and Biological activity of nojirimycin derived iminosugars

Polyhydroxylated nitrogen heterocycles, usually referred to as iminosugars, are known for their inhibitory activity toward carbohydrate-processing enzymes, suggesting their use in a wide range of potential therapeutic applications, such as treatment of diverse viral infections, such as human immunodeficiency virus (HIV), human hepatitis B virus (HBV), human hepatitis C (HCV), bovine viral diarrhea virus (BVDV), Japanese encephalitis virus (JEV) and dengue virus, as well as cancer, diabetes, tuberculosis, malaria and lysosomal storage diseases. Novel nojirimycin-derived bicyclic structures, containing cyclic carbamate, urea and guanidine moieties have been synthesised starting from suitably protected a-C-vinylnojirimycin and a-C-allylnojirimycin respectively, and their activity against different glycosidases tested. Biological activity of these iminosugars against bacterial toxins is currently under investigation.

Collaboration

Prof. Klaus Aktories at the Institute of Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-Universität,Freiburg[LC2] .

Antibacterial drug development inhibiting outer membrane biogenesis of gram-negative bacteria

Despite important advances made in the last century, infectious diseases caused by pathogenic microrganisms still are a major threat to human health. Thus, the necessity to develop new weapons against pathogenic bacteria is widely recognized as a major challenge for modern biomedical research. Protein targets involved in the outer membrane biogenesis of gram-negative bacteria are being exploited for the design and synthesis of novel inhibitors.

Collaboration

Prof. A. Polissi, Prof. L. De Gioia (this Department)
Prof. G. Deho’ and Prof. M. Bolognesi at the Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano
Dr. P. Mauri at the Istituto di Tecnologie Biomediche-CNR, Milano
Prof. A. Molinaro, University of Naples

NMR studies of receptor/ligand interactions.

NMR determination of SAR of PKB/Akt PH-domain and glucose-based inhibitors

Epitope mapping and NMR binding studies are currently being performed for glucose-based Akt inhibitors, in order to elucidate fundamental functional groups for interaction with the PH-domain of the target protein.

 Development of smart biomaterials

The generation of smart biomaterials for tissue engineering requires mimicking natural ECMs that regulate complex morphogenetic processes in tissue formation and regeneration. Their functionality should be adjustable to a particular biological environment to obtain cell- and tissue-specificity. Ideally, one would create them from an array of biocompatible scaffolds decorated with an array of ligands inducing cell adhesion and/or proliferation and/or differentiation. Several issues are taken into accounts for the design of bioactive and biocompatible materials: Ideally, the biomaterial should include cell-adhesive ligands (such as integrin-binding peptides of the prototypical RGD family or carbohydrates such as hialuronic acid), binding sites for growth factor (GF) proteins, domains with susceptibility to degradation by cell-secreted or cell-activated proteases to facilitate bidirectional cell-matrix interactions, but also domains with structural function (such as the elastin-derived peptide sequence VPGVG). The use of such synthetic approaches in “bioactive” material design may allow matrices to be tailor-made for a specific cell or tissue. In collaboration with research groups expert in material science and in stem cells, a research devoted to the functionalization biomaterial scaffolds with properly selected peptides and sugars is developed.

Dettagli Progetti di Ricerca

BIOCATALYSIS IN ORGANIC CHEMISTRY
Biocatalysis, use of enzymes as catalysts for chemical synthesis, has become a valuable tool for the synthetic chemist. Enzymatic transformations carried out by partially purified enzymes or whole-cell catalysts are used for the production of a wide variety of chemicals, from bulk to fine chemicals. The research at the Department focuses both on the use of enzymes as biocatalyst for a specific chemical transformation, in different reaction media, and on the development of new methods for identifying and isolating commercially useful enzymes from natural sources.
Partecipants: Cipolla Laura , La Ferla Barbara , Nicotra Francesco

CHEMICAL GENETICS
Chemical genetics combines chemistry with biology as a means of exploring the function of unknown proteins or identifying the proteins responsible for a particular phenotype. The chemical genetics approach that utilizes small molecules to modulate biological pathways plays a central role in the field of drug discovery and development. The ability of chemists to extend the repertoire of small molecules having interesting and oftentimes ‘unnatural’ properties is the prerequisite of chemical genetics. Using this ability, large number of possible molecules can be made, trying to explore regions of chemical space populated by molecules with interesting biological activity. This approach has being applied to the exploration of the function of novel protein targets.
Partecipants: Cipolla Laura , La Ferla Barbara , Nicotra Francesco , Peri Francesco

DEVELOPMENT OF NOVEL SYNTHETIC METHODOLOGIES
Bioorganic chemistry deals with molecules found in living organism which usually present a variety of functional groups. Chemical synthesis of these molecules or their analogues is particularly challenging, quite often requiring multistep syntheses biased by extensive and time-consuming protection/deprotection steps, and due to the complexity in manipulation. Novel synthetic methodologies that simplifies the synthetic procedures have been developed. Chemoselective ligation for peptide and glycopeptides assembly, neoglycosylation reactions for oligosaccharide and glycomimetic synthesis, microwave techniques for accelerating the reactions, are examples of developed methodologies. Particular attention is devoted to the development of reaction in aqueous solution, that are compatible with biological systems and environmental friendly.
Partecipants: Cipolla Laura , La Ferla Barbara , Nicotra Francesco , Peri Francesco

see also: BioOrganic Chemistry Group, PubMed, BOA, ResearchGate, ORCID, #BtBsPub

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Selected Recent Publications

– Maltose conjugation to PCL: Advanced structural characterization and preliminary biological properties
Valeria Secchi, Roberto Guizzardi, Laura Russo, Valentina Pastori, Marzia Lecchi, Stefano Franchi, Giovanna Iucci, Chiara Battocchio, Laura Cipolla
Journal of Molecular Structure Volume 1159, 5 May 2018, Pages 74-78 doi: 10.1016/j.molstruc.2018.01.051


– Convergent dendrimer synthesis by olefin metathesis and studies toward glycoconjugation
Roberto Guizzardi, Mattia Vacchini, Carlo Santambrogio, Laura Cipolla
Canadian Journal of Chemistry, 2017, 95(9): 1008-1012, https://doi.org/10.1139/cjc-2017-0146


– Functionalizing natural polymers with alkoxysilane coupling agents: reacting 3-glycidoxypropyl trimethoxysilane with poly(γ-glutamic acid) and gelatin
L. S. Connell, L. Gabrielli, O. Mahony, L. Russo, L. Cipolla and J. R. Jones
Polym. Chem., 2017, 8(6), 1095-1103. DOI: 10.1039/C6PY01425A

BOOKS
1. Blocking the anomeric reactivity, how and why. Francesco Nicotra, Laura Cipolla, Barbara La Ferla and Ana Catarina Araujo DOI: 10.1039/b000000x Specialist Periodical Reports: Carbohydrate Chemistry – Chemical and Biological Approaches . The Royal Society of Chemistry , 2009, 35, 259-288.
2. Materials biofunctionalization for tissue regeneration. Laura Cipolla, Laura Russo, Nasrin Shaikh, Francesco Nicotra POLYMERIC BIOMATERIALS III ED, Vol. I Polymers as Biomaterials CRC Press, 2010
3. Underexploited targets in LPS biogenenesis for the design of antibacterials Laura Cipolla,* Luca Gabrielli, Davide Bini, and Laura Russo CABI, Nosworthy Way, Wallingford OX10 8DE, UK. 2011, submitted.
4. Synthesis of C-glycosides from unprotected O-glycosides, Barbara La Ferla, Laura Cipolla, Wouter Hogendorf, Francesco Nicotra, Carbohydrate Chemistry-Proven Synthetic Methods, Ed. Paul Kovac, Taylor & Francis, vol 1,Chp 8 pp 83-89 (2011).
5.  Regioselective debenzylation of monosaccharide C-glycosides, Laura Cipolla, Barbara La Ferla, Francesco Nicotra, Carbohydrate Chemistry-Proven Synthetic Methods, Ed. Paul Kovac, Taylor & Francis, vol 1, cap 17 pp 167-173 (2011).
6. Materials biofunctionalization for tissue regeneration. Laura Cipolla, Laura Russo, Nasrin Shaikh, Francesco Nicotra POLYMERIC BIOMATERIALS III ED, Vol. I Polymers as Biomaterials CRC Press, 2010
7. Underexploited targets in LPS biogenenesis for the design of antibacterials Laura Cipolla,* Luca Gabrielli, Davide Bini, and Laura Russo CABI, Nosworthy Way, Wallingford OX10 8DE, UK. 2011, submitted.
8. Synthesis of C-glycosides from unprotected O-glycosides, Barbara La Ferla, Laura Cipolla, Wouter Hogendorf, Francesco Nicotra, Carbohydrate Chemistry-Proven Synthetic Methods, Ed. Paul Kovac, Taylor & Francis, vol 1,Chp 8 pp 83-89 (2011).
9.  Regioselective debenzylation of monosaccharide C-glycosides, Laura Cipolla, Barbara La Ferla, Francesco Nicotra, Carbohydrate Chemistry-Proven Synthetic Methods, Ed. Paul Kovac, Taylor & Francis, vol 1, cap 17 pp 167-173 (2011).
10. Trehalose mimetics as inhibitors of trehalose processing enzymes. Davide Bini, Francesca Cardona, Luca Gabrielli, Laura Russo, Laura Cipolla. Specialist Periodical Reports, SPR Carbohydrate Chemistry, Vol. 37, cap 10. Publisher: Royal Society of Chemistry (31 Dec 2011), DOI: 10.1039/9781849732765, ISBN-10: 1849731543.
11. Smart biomaterials: the contribution of glycoscience. Laura Cipolla,* Laura Russo, Francesca Taraballi, Cristina Lupo, Davide Bini, Luca Gabrielli, Alice Capitoli and Francesco Nicotra Specialist Periodical Reports, SPR Carbohydrate Chemistry, Vol. 38, cap 17. Publisher: Royal Society of Chemistry (31/8/2012). DOI: 10.1039/9781849734769-00416 ISBN: 9781849734394

APPLICATION ASSESOR for several international funding agencies:
NOW-Netherlands Organisation for Scientific Research-Chemical Sciences;
ANR-Agence Nationale de la Recherche (France), Chaires D’excellence» 2008 Research  Program.
BSAC -British Society for Antimicrobial Chemotherapy-Grants Program
IRCSET-Irish Research Council for Science, Engineering and Technology
INSPIRE: IRCSET-Marie Curie International Mobility Fellowships in Science Engineering  and Technology
EMPOWER: Government of Ireland Postdoctoral Fellowships in Science, Engineering and  Technology
FWF:-Austrian Science Fund
Agency for Science, Technology and Research (A*STAR) in Singapore
Panelist for the IRCSET-Irish Research Council for Science, Engineering and Technology

EDITORIAL ACTIVITY: –

Reviewer for international journals with editorial boards and indexed in ISI Web of Knowledge such as Carbohydrate Research, Journal of Organic Chemistry, European Journal of Organic Chemistry, European Journal of Medicinal Chemistry, Bioorganic & Medicinal Chemistry, Bioorganic & Medicinal Chemistry Lett., Medicinal Chemistry Communication (Royal Society of Chemistry), Drug Discovery Today, Expert Opinion on Therapeutic Patents (EOTP), Expert Opinion On Biological Therapy, and for the textbook “Chimica Organica”, edited by McGraw-Hill (Italy). -Guest Editor of the special issue titled “Role of Carbohydrates in tumor progression, metastasis and anti-tumor drug development” in Anti-Cancer Agents Bentham Sc. Publisher, 2008, Vol. 8, Issue 1 -Author for UNESCO Universal Enciclopedia EOLSS  www.eolss.net: “Chemistry of natural compounds” in  F. Nicotra (Ed.)  “Organic and Biomolecular Chemistry” 2006

SCIENTIFIC COLLABORATIONS:

Prof. Laura Cipolla has established several national and international colaborations: ● •Dr. A. Franco and Prof. H.M. Grey Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA, in a project devoted to immunological studies of MHCI/CTLs interactions with synthetic glycopeptides. ● •Dr. Jesus Jimenez-Barbero (Madrid, Spain) in the project  European Community’s Human Potential Programme under contract HPRN-CT-2002-00173 (“GLYCIDIC SCAFFOLDS”). ● •Prof. Lazzaroni at Pisa University, Dipartimento di Chimica e Chimica Industriale, in a project devoted to the synthesis of carbohydrate analogues via organometallic chemistry ● •Prof. Luigi Mandrich and Dr. Giuseppe Manco, Institute of Protein Biochemistry, CNR, Napoli in a project devoted to the study of a thermophilic esterase as novel biocatalyst in organic chemistry ● •ACS Dobfar S.p.A.- Metadistretti 2006 – ATI in the project “PANDA”( Peptide for Antibiotics and Nutraceuticals Design and Analysis). Sub-project: “Development of innovative biotechnological processes”. ● •Johannes Kepler University- Institute of Organic Chemistry(Linz, Upper Austria). REGINS 2005- Subproject INBIO: Stable enzymes as industrial catalysts. ● •Johannes Kepler University- Institute of Organic Chemistry(Linz, Upper Austria), University of Pavia-Department of Organic Chemistry.  REGINS – Subproject BIOCAT (INTERREG III C). ● Prof. Rodolfo Quarto, Dr Paolo Giannoni, Advanced Biotechnology Center, Genova, under project (progetto FIRB 2006, RBIP068JL9) ● Dr. Roberto de Santis, Institute for Composit and Biomedical Materials  (IMCB), Napoli under project (progetto FIRB 2006, RBIP068JL9) ● Prof. Julian R. Jones, Dept. of Materials, Imperial College, London UK ● Prof. Maurilio Marcacci, 3Laboratory of Biomechanics and Technology Innovation, Rizzoli Orthopaedic Institute, Bologna, Italy ● Prof. M. Valvano, Department of Microbiology and Immunology, University of Western Ontario ● Prof. R. Woodart, Department of Chemistry-University of Michigan (USA)

Team

Laura Cipolla – Head of lab – Associate Professor

office 4019, IV floor, building U3
tel: +39 02 6448 3460/3427
email: laura.cipolla@unimib.it
Curriculum vitae
see also: BioOrganic Chemistry Group, PubMed, BOA, ResearchGate, ORCID, #BtBsPub

Roberto Guizzardi – PhD student

room 4018, IV floor, building U3
tel: +39 02 6448 3427
r.guizzardi@campus.unimib.it
Curriculum vitae
 
Mattia Vacchini – PhD student

room 4018, IV floor, building U3
tel: +39 02 6448 3427
m.vacchini@campus.unimib.it
Curriculum vitae

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Current scientific interests

– Development of innovative smart biomaterials based on inorganic, organic or composite matrices for tissue regeneration
– Design and synthesis of several biologically active compounds, in particular carbohydrates and their structural analogues, and biologically relevant peptides and their mimetics
– Enzymes inhibitors of enzymes involved in relevant biological processes
– NMR studies for the elucidation of key details of ligand/receptor interactions
– Elucidation of molecular mechanism of key enzymes involved in physiological or pathological states

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Selected Recent Publications

– Maltose conjugation to PCL: Advanced structural characterization and preliminary biological properties
Valeria Secchi, Roberto Guizzardi, Laura Russo, Valentina Pastori, Marzia Lecchi, Stefano Franchi, Giovanna Iucci, Chiara Battocchio, Laura Cipolla
Journal of Molecular Structure Volume 1159, 5 May 2018, Pages 74-78 doi: 10.1016/j.molstruc.2018.01.051


– Convergent dendrimer synthesis by olefin metathesis and studies toward glycoconjugation
Roberto Guizzardi, Mattia Vacchini, Carlo Santambrogio, Laura Cipolla
Canadian Journal of Chemistry, 2017, 95(9): 1008-1012, https://doi.org/10.1139/cjc-2017-0146


– Functionalizing natural polymers with alkoxysilane coupling agents: reacting 3-glycidoxypropyl trimethoxysilane with poly(γ-glutamic acid) and gelatin
L. S. Connell, L. Gabrielli, O. Mahony, L. Russo, L. Cipolla and J. R. Jones
Polym. Chem., 2017, 8(6), 1095-1103. DOI: 10.1039/C6PY01425A