APIS Amino acids-Peptidomimetics-peptides-protein InteractionS

GRUPPO DI RICERCA
APIS group (Amino Acids – Peptidomimetics – Peptides – Protein Interactions)
Principal Investigator | Prof. Maria Luisa Gelmi |
Members | Prof. M. Luisa Gelmi, Prof. Alessandro Contini, Prof. Sara Pellegrino, Prof. Alessandra Romanelli, Dr. Raffaella Bucci |
Website | https://sites.unimi.it/apisgroup/ |
DESCRIPTION
Our group has multidisciplinary skills involving the design, synthesis and analytical / spectroscopic characterization of new amino acids, peptides, peptidomimetics and PNAs that can be used for various applications in the biomedical field but also as nanomaterials or catalysts.
1) Molecular modeling
The molecular modeling laboratory is aimed at studying phenomena at the interface between chemistry and biology. In particular, computational techniques are developed and applied to:
- study the modulation of pharmacologically relevant protein-protein interactions
- accurately predict binding energies
- design non-natural amino acids, able to stabilize particular secondary structures in peptide systems and study conformations of non-natural peptides
- predict optical (CD, VCD, OR) and spectroscopic (IR, NMR, UV) properties of organic / metallorganic molecules through quantum mechanical calculations
- development of computational methods for biomolecular modeling
2) Non-Natural Amino Acids
Non-natural amino acids, in particular conformationally rigid ones, thanks to their structure and the well-defined stereochemistry of their substituents, are interesting scaffolds for obtaining predefined molecular architectures. Our group has a long experience in the diastereo- and enantioselective synthesis of different classes of amino acids with a carbocyclic and heterocyclic structure, characterized by various substitution patterns that make them mimetics of natural amino acids. Their use is of particular relevance if inserted in peptide sequences as they are able to generate specific secondary structures (helices, turn, extended).
3) Peptides / Peptidomimetics
Microwave-assisted solid phase peptide synthesis (SPPS) is an innovative and particularly efficient synthetic approach for the preparation of difficult sequences. Using MW-SPPS technology, we synthesize small protein domains and peptide libraries for different applications.
The decrease in conformational freedom of an oligopeptide is a key step for obtaining peptidomimetics. The inclusion of non-natural amino acids and rigid scaffolds in the peptide sequence allows to modulate the molecular mobility and to define specific secondary structures. Starting from the library of compounds available in our laboratories, we design and synthesize new peptidomimetics. The investigation of the secondary structure of the new peptidomimetics is achieved through molecular modeling and conformational studies using NMR, IR and CD techniques.
The developed peptides and peptidomimetics find different applications such as:
- peptides modulators of protein-protein interactions. The presence of non-natural amino acids provides greater metabolic stability against proteases with considerable advantages for biomedical applications. Examples of applications include the modulation of the interaction between the Rac protein and its activators (GEF) or inhibitors (GAP), and the PFKFB3 protein involved in the glycolytic process.
- peptide-based pesticides with low environmental impact. In this context, peptide aptamers selected against fungal targets are developed as a new eco-compatible methodology and alternative to chemical pesticides for the protection of agricultural crops against oomycetes infections.
- antibacterial and antifungal peptides, of particular relevance, considering the growing onset of resistant bacterial strains. The ongoing projects are aimed at a) the design of more powerful molecules starting from natural peptides, through a rational approach that derives from the study of the structure-activity relationships of peptides; b) understanding the mechanism of action of peptides, through the study of peptide-cell interactions with spectroscopic methods.
- soft and hybrid nanomaterials and peptide-based nanofibers for biomedical applications such as the delivery of biologically active molecules
- peptide-metal hybrid catalysts for the study of enantio- and diastereoselective reactions
4) Peptide Nucleic Acids (PNA)
PNAs are oligonucleotide analogs characterized by a pseudo - peptide scaffold. PNAs can bind complementary DNA, RNA and PNA with high affinity and specificity. Thus, they have been extensively investigated as tools for modulating the expression of target genes. On the other hand, very few studies are reported in the literature on the aggregation properties of PNAs. The goal of this project is to study how PNAs aggregate and characterize the aggregates structure and their spectroscopic properties to create new nanomaterials based on nucleic acids.
PROJECT
- 2018_ H2020-MSCA-ITN 2015 EJD-TubInTrain programme “Modulation of Tubulin-Protein Interactions: from Cancer to Neurodegeneration” PI Prof. Passarella (Università Milano). Partecipanti: Prof. Gelmi, Prof. Clerici, Prof. Pellegrino
- 2018_H2020-FETOPEN-“NOPEST_Novel Pesticides for a Sustainable Agriculture” PI Prof. Pesaresi (Università Milano). Partecipanti: Prof. Pellegrino
- 2017_Progetto Regione Lombardia - Bando Smart Fashion and Design. “From waste to Green Fashion: similpelle vegetale da scarti di arance; ORANGE LEATHER (O1.2016.0008057) 2017 Responsabile Unità Prof. Gelmi, Partecipanti: Prof. Clerici, Prof. Pellegrino, Prof. Romanelli, Dr. Erba, Dr. Bucci
- 2015_ H2020-MSCA-ITN 2015 EJD-MOGLYNET programme “Modulation of glycolytic flux as a new approach for treatment of atherosclerosis and plaque stabilization: a multidisciplinary study” PI Prof. Gelmi. Partecipanti: Prof. Clerici, Prof. Contini, Prof. Pellegrino
- 2015_Progetto Prin: “Tumor-targeting peptidomimetics: synthesis and bio-medical applications ”Anno 2015-2011 – (Prot. 20157WW5EH). PI Prof. Gennari (Università Milano). Partecipanti: Prof. Gelmi, Prof. Contini
ONGOING RESEARCH COLLABORATIONS
- Université Paris Sud, BioCIS UMR 8076, LabEx LERMIT, Châtenay-Malabry (Prof. S. Ongeri)
- Universität Regensburg, Institut für Organische Chemie (Prof. O. Reiser)
- The Hebrew University of Jerusalem, Institute of Chemistry, Jerusalem (Prof. M. Reches)
- Faculty of Pharmacy, Assiut University (Prof. T. A.-F. Mohammad Hassan)
- Karolinska Institutet, Sweden (Prof. A. Achour)
- CIC nanoGUNE, San Sebastian Spain (Dr. A. Bittner)
- Dr. Barry Hardy, Douglas Connect (collaborazione nell'ambito del research network SAM, http://scientistsagainstmalaria.net/)
- Università degli Studi di Padova, Dipartimento di Farmacologia, (Prof. N. Ferri)
- Università degli Studi di Padova, Dipartimento di Chimica (Prof. F. Formaggio)
- Università degli Studi di Parma, Dipartimento di Biochimica e Biologia Molecolare (Prof. L. Ronda)
- The EBRI Institute (Dr. M. Feligioni)
- Università degli Studi di Torino, Dipartimento di Biotecnologie Molecolari e Scienze per la Salute (Prof. G. Merlo)
- Università degli Studi di Pavia, Dipartimento di Scienze del Farmaco (Prof. I. Genta)
- Innsbruck Medical University Biocenter Prof. F. Marx-Ladurner
- Università di Napoli “Federico II”, Dott.ssa A. Accardo, Prof.ssa F. Quaglia
- Génie Enzymatique et Cellulaire, Centre de Recherche de Royallieu, Sorbonne Universités, Université de Technologie de Compiègne, Compiègne, France, Dr. I. Maffucci
- Indena S.P.A
- Dr. B. Hardy, Edelweiss Connect GmbH (eCheminfo community of practice, https://www.echeminfo.com/)