Cyclic Peptoids in Drug Discovery: Antimicrobial, Antitumor and Immunomodulating Candidates (CyPDRUGS)
Antimicrobial, Antitumor, and Immunomodulating Candidates
MUR code: P2022ZBNC2; CUP: D53D23017270001
Project Overview
The CyPDRUGS project (“Cyclic peptoids in drug discovery: antimicrobial, antitumor and immunomodulating candidates”) is a 24-month multidisciplinary research initiative. This project is funded by the European Union under the NextGenerationEU program and by the Italian Ministry of University and Research (MUR) through the PRIN 2022 PNRR grant. The project began on December 1, 2023, and ended in February 2026, thanks to a 3-month extension.
Our mission is to expand the chemical diversity available for drug discovery to address global health threats, such as multidrug-resistant (MDR) pathogens, cancer, and immune system-related diseases.
Why Cyclic Peptoids?
Peptoids are a unique class of synthetic peptidomimetics where the side chains are linked to the nitrogen atom rather than the alpha-carbon. When these structures are cyclized, they offer several important advantages over traditional peptides:
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Enhanced Stability: They possess superior resistance to enzymatic and proteolytic degradation.
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Improved Bioavailability: The cyclic structure increases cell permeability.
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The Macrocyclic Effect: Cyclization reduces conformational flexibility, creating a stable 3D scaffold that is more effective for molecular recognition and mimicking biological processes.
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Versatile Synthesis: They are produced via a straightforward and solid-phase sub-monomer approach that allows for vast chemical diversity without the need for complex protective groups ( a green aspect).
Our Research Objectives
The project is divided into two primary objectives supported by five integrated Work Packages (WPs):
Objective 1: Design and Synthesis
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WP1: Knowledge-Based Drug Design: Utilizing in-silico tools (PDB/CSD databases) and bio-inspiration from natural antimicrobial peptides (AMPs) found in marine invertebrates and mammals to design target compounds.
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WP2: Synthesis and Characterization: Producing new linear and cyclic peptoids using advanced solid-phase techniques and characterizing their structures through NMR and X-ray diffraction.
Objective 2: Biological Validation
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WP3: Antimicrobial Evaluation: Testing compounds against a library of Gram-negative and Gram-positive laboratory strains and clinical isolates (including Pseudomonas aeruginosa from cystic fibrosis patients) to evaluate MIC, MBC, and antibiofilm activity.
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WP4: Antitumor Activity: Studying selective toxicity on human tumor cells (lung, breast, colorectal) and investigating cellular signaling pathways (MAPK, AKT) and apoptotic markers.
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WP5: Immunomodulatory Properties: Analyzing how these compounds interact with the innate immune system using human primary monocytes and macrophages to evaluate inflammatory responses and intracellular killing.
Expected Impact & Innovation
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Combatting MDR: Discovering new antimicrobial structures to fight the top global public health threat of antibiotic resistance.
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Therapeutic Innovation: Developing candidates for combined therapies that stimulate the immune response while treating infections or cancer.
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Scientific Reinforcement: Strengthening a network of excellence between organic synthesis, biochemistry, and immunology.
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Industrial Collaboration: Bridging academic research with the pharmaceutical industry to translate discoveries into clinical applications.
The Research Team
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The project unites three centers of excellence in the Campania region:
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RU1: University of Salerno (Lead) – Led by Prof. Irene Izzo (Principal Investigator), focusing on synthesis and structural characterization.
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RU2: University of Naples Federico II – Led by Prof. Eliodoro Pizzo, focusing on biochemistry and antimicrobial evaluation. https://www.docenti.unina.it/eliodoro.pizzo
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RU3: CNR - Institute of Biochemistry and Cell Biology (IBBC) – Led by Dr. Paola Italiani, focusing on immunology and inflammation. http://www.ibbc.cnr.it/researchers/paola-italiani/ ; https://immunologi.cnr.it/the-network/campania/innate-immunity-inflammation-and-nanosafety/
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Two young researchers (female) have been recruited thanks to the project: Dr. Vittoria Ferrara (RU1 UNISA): viferrara@unisa.it and Dr. Rosanna Culurciello (RU2 UNINA): rosanna.culurciello@unina.it
Contact Information
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Principal Investigator: Prof. Irene Izzo
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Sito Web: docenti.unisa.it/irene-izzo
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Email: iizzo@unisa.it
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This project is funded by the European Union – NextGenerationEU and the Ministry of University and Research under the PRIN 2022 PNRR program.
Complete list of poster and oral communications presented during the realization of the overall project
Prof. Irene Izzo presented the following contributions at national and international meetings.
Invited lecture: International Oligonucleotides and Peptides Conference” (IOPC), Milano 24-26 Giugno 2024.
Authors: Izzo, I.
Title:Cyclic peptoids: an intriguing class of macrocyclic peptidomimetics
This meeting is the forefront event for Oligonucleotides and Peptides innovation, regulatory and market trends. (Speaker and Attendance certificate – All. 2 and 3). This project, devoted to the search of new antimicrobial peptoids, was one of the topics reported during the presentation.
Invited lecture: Syn Open – Shenzhen University- Lectures 2025 (parte del Roadshow 2025 organizzato da Thieme in Cina): Izzo I. Cyclic Peptoids: from Structure to Properties, 16 Dicembre 2025, Shenzhen
Invited lecture: Thieme Symposium – University of Technology of Guangzhou (parte del Roadshow 2025 organizzato da Thieme in Cina) Izzo I. Cyclic Peptoids: from Structure to Properties, 17 Dicembre 2025, Guangzhou
Invited lecture: Thieme – HKUST organic Chemistry Symposium 2025, presso The Hong Kong University of Science and Technology (parte del Roadshow 2025 organizzato da Thieme in Cina): Izzo I. Cyclic Peptoids: from Structure to Properties, 19 Dicembre 2025, Hong Kong
Invited lecture: European Peptide Synthesis Conference (EPSC) 2025”, Porto, 25-27 Agosto 2025, Izzo I. “Macrocyclic peptidomimetics: structures and properties
Prof. Consiglia Tedesco presented the following contributions at international/national meetings:
Keynote speaker: 17th International Seminar on Inclusion Compounds and Porous Materials (ISIC2017), 2-6 September 2024, Poznan, Poland
Authors: G. Pierri, R. Schettini, F. De Riccardis, I. Izzo, C. Tedesco
Title: Molecular conformation, self-assembly, host-guest chemistry of cyclic peptoids
Oral communication: 12th Peptoid Summit, Berkeley, USA, 7-9 Agosto 2024.
Authors: C. Tedesco, G. Pierri, R. Schettini, N. D’Arminio, A. Marabotti, F. De Riccardis, I. Izzo
Title: The peptoids'outlook to intramolecular and intermolecular interactions
Oral communication: 18th Naples Workshop on Bioactive peptides
Authors: C. Tedesco, G. Pierri, R. Schettini, N. D’Arminio, F. L. Damiani, A. Marabotti, F. De Riccardis, I. Izzo
Title: From cyclic peptoids to beta turn in proteins
Poster communication: 34th European Crystallographic Meeting -ECM34, Padova, Italia, 25-30 Agosto 2024.
Authors: C. Tedesco, G. Pierri, N. D’Arminio, R. Schettini, A. Marabotti, F. De Riccardis, I. Izzo
Title: The peptoids’ path to understand the role of CH‧‧‧OC and CO‧‧‧CO interactions in proteins
Keynote speaker: MS28 Chemical Bonding and Molecular Structure at the 35th European Crystallographic Meeting (ECM35), August 25th-29th 2025, Poznan, Poland.
Authors: C. Tedesco, F. Damiani, G. Pierri, N. D’Arminio, A. Marabotti, F. De Riccardis, I. Izzo
Title: β-Turns, Peptides, Peptoids and CO‧‧‧CO interactions
To be published in a special issue of Acta Crystallographica A.
Invited lecture: 35th European Crystallographic Meeting (ECM35), August 25th-29th 2025,
Poznan, Poland
Authors: C. Tedesco, F. Damiani, G. Pierri, N. D’Arminio, A. Marabotti, F. De Riccardis, I.
Izzo
Title: “β-Turns, Peptides, Peptoids and CO‧‧‧CO interactions”
Poster Presentation: 51 st Meeting of the Italian Association of Crystallography, September 2nd-5th 2025, Firenze, Italy
Authors: F. Damiani, G. Pierri, C. Tedesco
Title: “Novel X-ray crystal structures of ThT”
Dr. Rosanna Culurciello and Prof Elio Pizzo presented the following contributions at national and international meetings.
Oral communication: the 11th International Meeting on Antimicrobial Peptides (IMAP 2024) - King’s College London, UK, 2-4 September 2024.
Authors: Di Nardo,I. Bosso, A.; Culurciello, R.; Palumbo, I.; D’Amato, A.; De Riccardis F.; Izzo, I.; Merola, M.; Cafaro, V.; Pizzo, E.; Notomista, E.; Veldhuizen, E. J.A.
Title: P13#1, an antimicrobial peptoid mimicking short cathelicidins with promising immunomodulatory activities on murine macrophages Raw 264.7.
Poster communication: 22nd Convention of investigators in cystic fibrosis; Centro congressi camera di commercio, Corso Porta Nuova, 96 – Verona, Italy; 14-16 November 2024.
Authors: Di Nardo,I. Bosso, A.; Culurciello, R.; Palumbo, I.; Cafaro, V.; Savadi P.; Casale, A.
Vendemia, V.; Schettini, R.;Merola, M.; De Riccardis F.; Izzo, I.; Pizzo, E.; Ungaro, F.;D’Angelo I.; Notomista, E.
Title: Inhalable nanoparticles delivering peptidomimetic/antibiotic combinations for local treatmentof CF lung infections – FFC#8/2023”.
Oral communication: 1st SIB Young Meeting 202, 25-27 March 2026, Abano Terme, Italia.
Title: CyP13#1, a new cyclic peptoid inspired by its linear analogue P13#1
Authors: Palumbo I., Di Nardo I., Cristiano M., Culurciello R., Bosso A., Izzo I., Cafaro V., Pizzo E., Notomista E.
Dr. Vittoria Ferrara presented the following contributions at national and international meetings.
Poster communication: Supramolecular Chemistry Days for Young Researchers 2025, Salerno 11-13 June 2025.
Authors: V. Ferrara, R. Mauro, R. Schettini, W. Cieślik, P. Zioła, A. Mrozek-Wilczkiewicz, O. Janďourek, M. Doležal, G. Della Sala, F. De Riccardis, I. Izzo.
Title: Synthesis and ionophoric properties of proline-rich cyclic peptoids.
Oral communication: Il Contributo dei Giovani Chimici in Campania – Edizione 2025. Salerno, 3-4 July 2025.
Authors: V. Ferrara, R. Schettini, E. Notomista, E. Pizzo, P. Italiani, F. De Riccardis, G. Della Sala, I. Izzo.
Title: Synthesis of cyclic peptoids with potential antimicrobial activities
Poster communication: European Peptide Synthesis Conference 2025, 25-27 August 2025, Porto, Portugal.
Title: Synthesis of proline-rich cyclic peptoids with biological activities
Authors: Ferrara V., Mauro R., Schettini R., Cieślik W., Zioła P., Mrozek-Wilczkiewicz A., Janďourek O., Doležal M., Della Sala G., De Riccardis F., Izzo I.
Oral communication: XLII Convegno Nazionale della Chimica Organica della Società Chimica Italiana, 21-25 September 2025, Cagliari, Italy.
Title: Synthesis of bioactive proline-rich cyclic peptoids.
Authors: Ferrara V., Mauro R., Schettini R., Cieślik W., Zioła P., Mrozek-Wilczkiewicz A., Janďourek O., Doležal M., Della Sala G., De Riccardis F., Izzo I.