8 results on '"Rosa Bellavita"'
Search Results
2. First-in-Class Cyclic Temporin L Analogue: Design, Synthesis, and Antimicrobial Assessment
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Bruno Casciaro, Salvatore Di Maro, Floriana Cappiello, Stefania Galdiero, Alfonso Carotenuto, Maria Luisa Mangoni, Diego Brancaccio, Francesco Merlino, Tom N. Grossmann, Ettore Novellino, Paolo Grieco, Rosa Bellavita, Annarita Falanga, Elisabetta Buommino, Organic Chemistry, AIMMS, Bellavita, R., Casciaro, B., Di Maro, S., Brancaccio, D., Carotenuto, A., Falanga, A., Cappiello, F., Buommino, E., Galdiero, S., Novellino, E., Grossmann, T. N., Mangoni, M. L., Merlino, F., and Grieco, P.
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Cell Survival ,Stereochemistry ,Rana temporaria ,Antimicrobial peptides ,Antineoplastic Agents ,Microbial Sensitivity Tests ,Article ,Antineoplastic Agent ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Anti-Bacterial Agent ,Drug Discovery ,Animals ,Humans ,Cell Proliferation ,chemistry.chemical_classification ,Antimicrobial Cationic Peptide ,Bacteria ,Dose-Response Relationship, Drug ,Molecular Structure ,Animal ,Microbial Sensitivity Test ,Disulfide bond ,cyclic peptides ,Biological activity ,Antimicrobial ,Temporin ,Cyclic peptide ,Anti-Bacterial Agents ,temporin L ,chemistry ,Design synthesis ,Drug Design ,Lactam ,Molecular Medicine ,Drug Screening Assays, Antitumor ,SDG 6 - Clean Water and Sanitation ,Human ,Antimicrobial Cationic Peptides - Abstract
The pharmacodynamic and pharmacokinetic properties of bioactive peptides can be modulated by introducing conformational constraints such as intramolecular macrocyclizations, which can involve either the backbone and/or side chains. Herein, we aimed at increasing the α-helicity content of temporin L, an isoform of an intriguing class of linear antimicrobial peptides (AMPs), endowed with a wide antimicrobial spectrum, by the employment of diverse side-chain tethering strategies, including lactam, 1,4-substituted [1,2,3]-triazole, hydrocarbon, and disulfide linkers. Our approach resulted in a library of cyclic temporin L analogues that were biologically assessed for their antimicrobial, cytotoxic, and antibiofilm activities, leading to the development of the first-in-class cyclic peptide related to this AMP family. Our results allowed us to expand the knowledge regarding the relationship between the α-helical character of temporin derivatives and their biological activity, paving the way for the development of improved antibiotic cyclic AMP analogues.
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- 2021
3. Broad-Spectrum Antiviral Activity of the Amphibian Antimicrobial Peptide Temporin L and Its Analogs
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Carla Zannella, Annalisa Chianese, Luciana Palomba, Maria Elena Marcocci, Rosa Bellavita, Francesco Merlino, Paolo Grieco, Veronica Folliero, Anna De Filippis, Marialuisa Mangoni, Lucia Nencioni, Gianluigi Franci, Massimiliano Galdiero, Zannella, Carla, Chianese, Annalisa, Palomba, Luciana, Marcocci, Maria Elena, Bellavita, Rosa, Merlino, Francesco, Grieco, Paolo, Folliero, Veronica, De Filippis, Anna, Mangoni, Marialuisa, Nencioni, Lucia, Franci, Gianluigi, Galdiero, Massimiliano, Zannella, C., Chianese, A., Palomba, L., Marcocci, M. E., Bellavita, R., Merlino, F., Grieco, P., Folliero, V., De Filippis, A., Mangoni, M., Nencioni, L., Franci, G., and Galdiero, M.
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antimicrobial peptide ,Cell Survival ,amps ,temporin ,frog peptides ,Amphibian Protein ,Gram-Positive Bacteria ,Antiviral Agents ,Chlorocebus aethiop ,Catalysis ,Amphibian Proteins ,Inorganic Chemistry ,Amphibians ,antimicrobial peptides ,AMPs ,Antimicrobial peptides ,Antiviral activity ,Frog peptides ,HSV-1 ,SARS-CoV-2 ,Temporins ,Virus-host interaction ,Amino Acid Sequence ,Animals ,Antimicrobial Cationic Peptides ,Chlorocebus aethiops ,DNA Viruses ,Gram-Negative Bacteria ,Humans ,Lipids ,RNA Viruses ,Vero Cells ,Physical and Theoretical Chemistry ,temporins ,antiviral activity ,virus-host interaction ,hsv-1 ,sars-cov-2 ,Molecular Biology ,Spectroscopy ,AMP ,Antiviral Agent ,RNA Viruse ,Antimicrobial Cationic Peptide ,Animal ,Organic Chemistry ,General Medicine ,Amphibian ,Lipid ,Computer Science Applications ,frog peptide ,DNA Viruse ,Human - Abstract
The COVID-19 pandemic has evidenced the urgent need for the discovery of broad-spectrum antiviral therapies that could be deployed in the case of future emergence of novel viral threats, as well as to back up current therapeutic options in the case of drug resistance development. Most current antivirals are directed to inhibit specific viruses since these therapeutic molecules are designed to act on a specific viral target with the objective of interfering with a precise step in the replication cycle. Therefore, antimicrobial peptides (AMPs) have been identified as promising antiviral agents that could help to overcome this limitation and provide compounds able to act on more than a single viral family. We evaluated the antiviral activity of an amphibian peptide known for its strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, namely Temporin L (TL). Previous studies have revealed that TL is endowed with widespread antimicrobial activity and possesses marked haemolytic activity. Therefore, we analyzed TL and a previously identified TL derivative (Pro3, DLeu9 TL, where glutamine at position 3 is replaced with proline, and the D-Leucine enantiomer is present at position 9) as well as its analogs, for their activity against a wide panel of viruses comprising enveloped, naked, DNA and RNA viruses. We report significant inhibition activity against herpesviruses, paramyxoviruses, influenza virus and coronaviruses, including SARS-CoV-2. Moreover, we further modified our best candidate by lipidation and demonstrated a highly reduced cytotoxicity with improved antiviral effect. Our results show a potent and selective antiviral activity of TL peptides, indicating that the novel lipidated temporin-based antiviral agents could prove to be useful additions to current drugs in combatting rising drug resistance and epidemic/pandemic emergencies.
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- 2022
4. Novel temporin L antimicrobial peptides: promoting self-assembling by lipidic tags to tackle superbugs
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Floriana Cappiello, Stefania Galdieroa, Maria Luisa Mangoni, Francesco Merlino, Annarita Falanga, Paolo Grieco, Rossella Paolillo, Elisabetta Buommino, Rosa Bellavita, Maria Rosaria Catania, Ettore Novellino, Bruno Casciaro, Bellavita, R., Falanga, A., Buommino, E., Merlino, F., Casciaro, B., Cappiello, F., Mangoni, M. L., Novellino, E., Catania, M. R., Paolillo, R., Grieco, P., and Galdiero, S.
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Staphylococcus aureus ,Cell Survival ,Antimicrobial peptides ,Microbial Sensitivity Tests ,RM1-950 ,01 natural sciences ,Structure-Activity Relationship ,Membrane interaction ,Drug Discovery ,Self assembling ,Animals ,Humans ,Moiety ,membrane interaction ,Cells, Cultured ,Pharmacology ,Sheep ,Dose-Response Relationship, Drug ,Molecular Structure ,010405 organic chemistry ,Chemistry ,General Medicine ,Antimicrobial ,Combinatorial chemistry ,Temporin ,self-assembling ,Anti-Bacterial Agents ,0104 chemical sciences ,antimicrobial peptides (AMPs) ,Klebsiella pneumoniae ,010404 medicinal & biomolecular chemistry ,Membrane ,Proteolysis ,Pseudomonas aeruginosa ,temporin L analogues ,Therapeutics. Pharmacology ,Research Article ,Research Paper ,Antimicrobial Cationic Peptides - Abstract
The rapid development of antimicrobial resistance is pushing the search in the discovering of novel antimicrobial molecules to prevent and treat bacterial infections. Self-assembling antimicrobial peptides, as the lipidated peptides, are a novel and promising class of molecules capable of meeting this need. Based on previous work on Temporin L analogs, several new molecules lipidated at the N- or and the C-terminus were synthesised. Our goal is to improve membrane interactions through finely tuning self-assembly to reduce oligomerisation in aqueous solution and enhance self-assembly in bacterial membranes while reducing toxicity against human cells. The results here reported show that the length of the aliphatic moiety is a key factor to control target cell specificity and the oligomeric state of peptides either in aqueous solution or in a membrane-mimicking environment. The results of this study pave the way for the design of novel molecules with enhanced activities.
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- 2020
5. Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes
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Gustavo B. da Silva, Rosa Bellavita, Izabel Christina Nunes de Palmer Paixão, Stefania Galdiero, Viveca Giongo, S.G. De-Simone, Camilly P. Pires De Melo, Annarita Falanga, Giongo, Viveca, Falanga, Annarita, De Melo, Camilly P Pire, da Silva, Gustavo B, Bellavita, Rosa, De-Simone, Salvatore G, Paixão, Izabel C, and Galdiero, Stefania
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liposome drug carrier ,Cell Survival ,Pharmaceutical Science ,herpes simplex virus type 1 ,Herpesvirus 1, Human ,Pharmacology ,Chlorocebus aethiop ,Antiviral Agents ,Article ,Analytical Chemistry ,chemistry.chemical_compound ,QD241-441 ,Immune system ,Naphthoquinone ,In vivo ,Phosphatidylcholine ,Chlorocebus aethiops ,Drug Discovery ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Drug Carrier ,Vero Cells ,Cells, Cultured ,Antiviral Agent ,Drug Carriers ,Liposome ,Molecular Structure ,Animal ,Chemistry ,nanoparticle ,Organic Chemistry ,aminomethylnaphthoquinone ,medicine.disease ,Cold sore ,aminomethylnaphthoquinones ,Chemistry (miscellaneous) ,Liposomes ,Vero Cell ,Nanoparticles ,Molecular Medicine ,Amine gas treating ,Drug carrier ,Human ,Naphthoquinones - Abstract
HSV infections, both type 1 and type 2, are among the most widespread viral diseases affecting people of all ages. Their symptoms could be mild, with cold sores up to 10 days of infection, blindness and encephalitis caused by HSV-1 affecting immunocompetent and immunosuppressed individuals. The severe effects derive from co-evolution with the host, resulting in immune evasion mechanisms, including latency and growing resistance to acyclovir and derivatives. An efficient alternative to controlling the spreading of HSV mutations is the exploitation of new drugs, and the possibility of enhancing their delivery through the encapsulation of drugs into nanoparticles, such as liposomes. In this work, liposomes were loaded with a series of 2-aminomethyl- 3-hydroxy-1,4-naphthoquinones derivatives with n-butyl (compound 1), benzyl (compound 2) and nitrobenzene (compound 3) substituents in the primary amine of naphthoquinone. They were previously identified to have significant inhibitory activity against HSV-1. All of the aminomethylnaphthoquinones derivatives encapsulated in the phosphatidylcholine liposomes were able to control the early and late phases of HSV-1 replication, especially those substituted with the benzyl (compound 2) and nitrobenzene (compound 3), which yields selective index values that are almost nine times more efficient than acyclovir. The growing interest of the industry in topical administration against HSV supports our choice of liposome as a drug carrier of aminomethylnaphthoquinones derivatives for formulations of in vivo pre-clinical assays.
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- 2021
6. Functional Selectivity Revealed by N-Methylation Scanning of Human Urotensin II and Related Peptides
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Alfonso Carotenuto, Paolo Grieco, William D. Lubell, Rosa Bellavita, Ettore Novellino, Etienne Billard, Diego Brancaccio, Paola Santicioli, Ali Munaim Yousif, David Chatenet, Salvatore Di Maro, Terence E. Hébert, Roberta d'Emmanuele di Villa Bianca, Francesco Merlino, Luigi Abate, Luciana Marinelli, Merlino, F., Billard, E., Yousif, A. M., Di Maro, S., Brancaccio, D., Abate, L., Carotenuto, A., Bellavita, R., D'Emmanuele Di Villa Bianca, R., Santicioli, P., Marinelli, L., Novellino, E., Hebert, T. E., Lubell, W. D., Chatenet, D., Grieco, P., Merlino, Francesco, Billard, Etienne, Yousif, Ali Munaim, Di Maro, Salvatore, Brancaccio, Diego, Abate, Luigi, Carotenuto, Alfonso, Bellavita, Rosa, d'Emmanuele di Villa Bianca, Roberta, Santicioli, Paolo, Marinelli, Luciana, Novellino, Ettore, Hébert, Terence, Lubell, William D, Chatenet, David, Grieco, Paolo, University of Naples Federico II, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Menarini Ricerche [Florence], McGill University = Université McGill [Montréal, Canada], Université de Montréal (UdeM), and The study was supported by Canadian Institutes of Health Research (CIHR) (MOP-142184) and the Natural Sciences and Engineering Research Council of Canada (NSERC) (RGPIN-2015-04848) to D.C. We thank the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC) for funding
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Untranslated region ,Male ,Protein Conformation ,[SDV]Life Sciences [q-bio] ,Peptide Hormones ,Urotensins ,Peptide ,CHO Cells ,Urotensin-II receptor ,Ligands ,01 natural sciences ,Methylation ,Receptors, G-Protein-Coupled ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Protein structure ,Cricetulus ,Drug Discovery ,Urotensin-II, peptide synthesis, NMR spectroscopy, N-methylation ,Functional selectivity ,Animals ,Humans ,Nuclear Magnetic Resonance, Biomolecular ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Intracellular Signaling Peptides and Proteins ,Biological activity ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,HEK293 Cells ,chemistry ,Biochemistry ,Molecular Medicine ,Urotensin-II - Abstract
International audience; In accordance with their common but also divergent physiological actions, human urotensin II (1) and urotensin II-related peptide (2) could stabilize specific urotensin II receptor (UTR) conformations, thereby activating different signaling pathways, a feature referred to as biased agonism or functional selectivity. Sequential N-methylation of the amides in the conserved core sequence of 1, 2, and fragment U-II4-11 (3) shed light on structural requirements involved in their functional selectivity. Thus, 18 N-methylated UTR ligands were synthesized and their biological profiles evaluated using in vitro competition binding assays, ex vivo rat aortic ring bioassays and BRET-based biosensor experiments. Biological activity diverged from that of the parent structures contingent on the location of amide methylation, indicating relevant hydrogen-bond interactions for the function of the endogenous peptides. Conformational analysis of selected N-methyl analogs indicated the importance of specific amide residues of 2 for the distinct pharmacology relative to 1 and 3.
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- 2019
7. The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin-L
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Paolo Grieco, Elisabetta Buommino, Diego Brancaccio, Bruno Casciaro, Ignazio Antignano, Francesca Paola Nocera, Ettore Novellino, Alfonso Carotenuto, Daniela Roversi, Maria Rosa Loffredo, Elisabetta Bianchi, Maria Luisa Mangoni, Rosa Bellavita, Francesco Merlino, Raffaele Ingenito, Pasqualina Punzi, Buommino, E., Carotenuto, A., Antignano, Mariarosaria, Bellavita, R., Casciaro, Raffaella, Loffredo, MARIA ROSARIA, Merlino, F., Novellino, E., Mangoni, M. L., Nocera, F. P., Brancaccio, D., Punzi, P., Roversi, D., Ingenito, R., Bianchi, E., and Grieco, P.
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Circular dichroism ,Magnetic Resonance Spectroscopy ,Proline ,antimicrobial peptide ,Stereochemistry ,Antimicrobial peptides ,biological activity ,Microbial Sensitivity Tests ,Gram-Positive Bacteria ,Hemolysis ,01 natural sciences ,Biochemistry ,Protein Structure, Secondary ,antimicrobial peptides ,conformational studies ,synthesis ,temporin L analogues ,Pyrrolidine ,Structure-Activity Relationship ,chemistry.chemical_compound ,Anti-Infective Agents ,Candida albicans ,Gram-Negative Bacteria ,Drug Discovery ,Humans ,Amino Acid Sequence ,General Pharmacology, Toxicology and Pharmaceutics ,Cytotoxicity ,Pharmacology ,010405 organic chemistry ,Circular Dichroism ,Organic Chemistry ,Proteins ,Biological activity ,Antimicrobial ,Temporin ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,conformational studie ,Molecular Medicine ,synthesi ,Antimicrobial Cationic Peptides - Abstract
Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro3 ]TL, in which glutamine at position 3 was substituted with proline. In this study, a series of analogues in which position 3 is substituted with non-natural proline derivatives, was investigated for correlations between the conformational properties of the compounds and their antibacterial, cytotoxic, and hemolytic activities. Non-natural proline analogues with substituents at position 4 of the pyrrolidine ring were considered. Structure-activity relationship (SAR) studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with circular dichroism (CD) and NMR spectroscopic analyses for selected compounds. The most promising peptides were additionally evaluated for their activity against some representative veterinary microbial strains to compare with those from human strains. We identified novel analogues with interesting properties that make them attractive lead compounds.
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- 2019
8. Urokinase receptor derived peptides as potent inhibitors of the formyl peptide receptor type 1-triggered cell migration
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Ali Munaim Yousif, Michele Minopoli, Ettore Novellino, Francesco Merlino, Alfonso Carotenuto, Diego Brancaccio, Paolo Grieco, Rosa Bellavita, Vincenzo Ingangi, Maria Vincenza Carriero, Yousif, Ali Munaim, Ingangi, Vincenzo, Merlino, Francesco, Brancaccio, Diego, Minopoli, Michele, Bellavita, Rosa, Novellino, Ettore, Carriero, Maria Vincenza, Carotenuto, Alfonso, and Grieco, Paolo
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0301 basic medicine ,Peptide ,Receptors, Urokinase Plasminogen Activator ,03 medical and health sciences ,Structure-Activity Relationship ,0302 clinical medicine ,Formyl peptide receptor ,Cell Movement ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,Receptor ,Peptide conformational analysi ,chemistry.chemical_classification ,Pharmacology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Animal ,Monocyte ,Peptide structure-activity relationship ,Drug Discovery3003 Pharmaceutical Science ,Organic Chemistry ,Chemotaxis ,Cell migration ,General Medicine ,Receptors, Formyl Peptide ,Rats ,Cell biology ,Urokinase receptor ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Rat ,Peptide inhibitors of cell migration ,Urokinase-type plasminogen activator receptor ,Pharmacophore ,Peptides ,Human - Abstract
The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration. We and others have previously documented that the uPAR(84–95) sequence, interacts with the formyl peptide receptors (FPR)s, henceforth inducing cell migration of several cell lines, including leukocytes, and the synthetic shorter peptide (Ser88-Arg-Ser-Arg-Tyr92, SRSRY) retains chemotactic activity in vitro and in vivo. Recently, we have developed the head-to-tail cyclic analog [SRSRY], a new potent and stable inhibitor of monocyte trafficking. This prompted us to develop novel cyclic and linear analogs of [SRSRY] with the aim to broaden the knowledge about structure-activity relationships of peptide [SRSRY]. Herein we report their synthesis, effects on cell migration, conformational and docking analyses which served to envisage a new pharmacophore model for inhibitors of FPR1-triggered cell migration.
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- 2018
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