Design of a Helical-Stabilized, Cyclic, and Nontoxic Analogue of the Peptide Cm-p5 with Improved Antifungal Activity

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversity of Havana-
Autor(es): dc.contributor25 and i-
Autor(es): dc.contributorCenter for Genetic Engineering and Biotechnology-
Autor(es): dc.contributorUniversity Clinic of Ulm-
Autor(es): dc.contributorUniversidad de Buenos Aires-
Autor(es): dc.contributorUniversidade Federal de São Carlos (UFSCar)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUlm University-
Autor(es): dc.creatorVicente, Fidel E. Morales-
Autor(es): dc.creatorGonzález-Garcia, Melaine-
Autor(es): dc.creatorDiaz Pico, Erbio-
Autor(es): dc.creatorMoreno-Castillo, Elena-
Autor(es): dc.creatorGaray, Hilda E.-
Autor(es): dc.creatorRosi, Pablo E.-
Autor(es): dc.creatorJimenez, Asiel Mena-
Autor(es): dc.creatorCampos-Delgado, Jose A.-
Autor(es): dc.creatorRivera, Daniel G.-
Autor(es): dc.creatorChinea, Glay-
Autor(es): dc.creatorPietro, Rosemeire C. L. R. [UNESP]-
Autor(es): dc.creatorStenger, Steffen-
Autor(es): dc.creatorSpellerberg, Barbara-
Autor(es): dc.creatorKubiczek, Dennis-
Autor(es): dc.creatorBodenberger, Nicholas-
Autor(es): dc.creatorDietz, Steffen-
Autor(es): dc.creatorRosenau, Frank-
Autor(es): dc.creatorPaixão, Márcio Weber-
Autor(es): dc.creatorStändker, Ludger-
Autor(es): dc.creatorOtero-González, Anselmo J.-
Data de aceite: dc.date.accessioned2022-02-22T00:27:52Z-
Data de disponibilização: dc.date.available2022-02-22T00:27:52Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2019-11-18-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1021/acsomega.9b02201-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/199624-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/199624-
Descrição: dc.descriptionFollowing the information obtained by a rational design study, a cyclic and helical-stabilized analogue of the peptide Cm-p5 was synthetized. The cyclic monomer showed an increased activity in vitro against Candida albicans and Candida parapsilosis, compared to Cm-p5. Initially, 14 mutants of Cm-p5 were synthesized following a rational design to improve the antifungal activity and pharmacological properties. Antimicrobial testing showed that the activity was lost in each of these 14 analogues, suggesting, as a main conclusion, that a Glu-His salt bridge could stabilize Cm-p5 helical conformation during the interaction with the plasma membrane. A derivative, obtained by substitution of Glu and His for Cys, was synthesized and oxidized with the generation of a cyclic monomer with improved antifungal activity. In addition, two dimers were generated during the oxidation procedure, a parallel and antiparallel one. The dimers showed a helical secondary structure in water, whereas the cyclic monomer only showed this conformation in SDS. Molecular dynamic simulations confirmed the helical stabilizations for all of them, therefore indicating the possible essential role of the Glu-His salt bridge. In addition, the antiparallel dimer showed a moderate activity against Pseudomonas aeruginosa and a significant activity against Listeria monocytogenes. Neither the cyclic monomer nor the dimers were toxic against macrophages or THP-1 human cells. Due to its increased capacity for fungal control compared to fluconazole, its low cytotoxicity, together with a stabilized α-helix and disulfide bridges, that may advance its metabolic stability, and in vivo activity, the new cyclic Cm-p5 monomer represents a potential systemic antifungal therapeutic candidate.-
Descrição: dc.descriptionGeneral Chemistry Department Faculty of Chemistry University of Havana, Zapata y G-
Descrição: dc.descriptionCenter for Natural Products Research Faculty of Chemistry University of Havana, Zapata y G-
Descrição: dc.descriptionCenter for Protein Studies Faculty of Biology University of Havana 25 and i-
Descrição: dc.descriptionSynthetic Peptides Group Center for Genetic Engineering and Biotechnology, P.O. Box 6162-
Descrição: dc.descriptionInstitute of Medical Microbiology and Hygiene University Clinic of Ulm, Robert Koch Str. 8-
Descrição: dc.descriptionDepartment of Inorganic Chemistry Analytical and Physical Chemistry Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires-
Descrição: dc.descriptionCenter of Excellence for Research in Sustainable Chemistry (CERSusChem) Department of Chemistry Federal University of São Carlos-UFSCar-
Descrição: dc.descriptionLaboratory of Pharmaceutical Biotechnology Department of Drugs and Medicines School of Pharmaceutical Sciences UNESP-
Descrição: dc.descriptionCore Facility for Functional Peptidomics Ulm Peptide Pharmaceuticals (U-PEP) University Ulm Faculty of Medicine Ulm University-
Descrição: dc.descriptionInstitute of Pharmaceutical Biotechnology Ulm University, James-Frank-Ring N27-
Descrição: dc.descriptionLaboratory of Pharmaceutical Biotechnology Department of Drugs and Medicines School of Pharmaceutical Sciences UNESP-
Formato: dc.format19081-19095-
Idioma: dc.languageen-
Relação: dc.relationACS Omega-
???dc.source???: dc.sourceScopus-
Título: dc.titleDesign of a Helical-Stabilized, Cyclic, and Nontoxic Analogue of the Peptide Cm-p5 with Improved Antifungal Activity-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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