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Metadados | Descrição | Idioma |
---|---|---|
Autor(es): dc.contributor | University of Havana | - |
Autor(es): dc.contributor | 25 and i | - |
Autor(es): dc.contributor | Center for Genetic Engineering and Biotechnology | - |
Autor(es): dc.contributor | University Clinic of Ulm | - |
Autor(es): dc.contributor | Universidad de Buenos Aires | - |
Autor(es): dc.contributor | Universidade Federal de São Carlos (UFSCar) | - |
Autor(es): dc.contributor | Universidade Estadual Paulista (Unesp) | - |
Autor(es): dc.contributor | Ulm University | - |
Autor(es): dc.creator | Vicente, Fidel E. Morales | - |
Autor(es): dc.creator | González-Garcia, Melaine | - |
Autor(es): dc.creator | Diaz Pico, Erbio | - |
Autor(es): dc.creator | Moreno-Castillo, Elena | - |
Autor(es): dc.creator | Garay, Hilda E. | - |
Autor(es): dc.creator | Rosi, Pablo E. | - |
Autor(es): dc.creator | Jimenez, Asiel Mena | - |
Autor(es): dc.creator | Campos-Delgado, Jose A. | - |
Autor(es): dc.creator | Rivera, Daniel G. | - |
Autor(es): dc.creator | Chinea, Glay | - |
Autor(es): dc.creator | Pietro, Rosemeire C. L. R. [UNESP] | - |
Autor(es): dc.creator | Stenger, Steffen | - |
Autor(es): dc.creator | Spellerberg, Barbara | - |
Autor(es): dc.creator | Kubiczek, Dennis | - |
Autor(es): dc.creator | Bodenberger, Nicholas | - |
Autor(es): dc.creator | Dietz, Steffen | - |
Autor(es): dc.creator | Rosenau, Frank | - |
Autor(es): dc.creator | Paixão, Márcio Weber | - |
Autor(es): dc.creator | Ständker, Ludger | - |
Autor(es): dc.creator | Otero-González, Anselmo J. | - |
Data de aceite: dc.date.accessioned | 2022-02-22T00:27:52Z | - |
Data de disponibilização: dc.date.available | 2022-02-22T00:27:52Z | - |
Data de envio: dc.date.issued | 2020-12-11 | - |
Data de envio: dc.date.issued | 2020-12-11 | - |
Data de envio: dc.date.issued | 2019-11-18 | - |
Fonte completa do material: dc.identifier | http://dx.doi.org/10.1021/acsomega.9b02201 | - |
Fonte completa do material: dc.identifier | http://hdl.handle.net/11449/199624 | - |
Fonte: dc.identifier.uri | http://educapes.capes.gov.br/handle/11449/199624 | - |
Descrição: dc.description | Following 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.description | General Chemistry Department Faculty of Chemistry University of Havana, Zapata y G | - |
Descrição: dc.description | Center for Natural Products Research Faculty of Chemistry University of Havana, Zapata y G | - |
Descrição: dc.description | Center for Protein Studies Faculty of Biology University of Havana 25 and i | - |
Descrição: dc.description | Synthetic Peptides Group Center for Genetic Engineering and Biotechnology, P.O. Box 6162 | - |
Descrição: dc.description | Institute of Medical Microbiology and Hygiene University Clinic of Ulm, Robert Koch Str. 8 | - |
Descrição: dc.description | Department of Inorganic Chemistry Analytical and Physical Chemistry Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires | - |
Descrição: dc.description | Center of Excellence for Research in Sustainable Chemistry (CERSusChem) Department of Chemistry Federal University of São Carlos-UFSCar | - |
Descrição: dc.description | Laboratory of Pharmaceutical Biotechnology Department of Drugs and Medicines School of Pharmaceutical Sciences UNESP | - |
Descrição: dc.description | Core Facility for Functional Peptidomics Ulm Peptide Pharmaceuticals (U-PEP) University Ulm Faculty of Medicine Ulm University | - |
Descrição: dc.description | Institute of Pharmaceutical Biotechnology Ulm University, James-Frank-Ring N27 | - |
Descrição: dc.description | Laboratory of Pharmaceutical Biotechnology Department of Drugs and Medicines School of Pharmaceutical Sciences UNESP | - |
Formato: dc.format | 19081-19095 | - |
Idioma: dc.language | en | - |
Relação: dc.relation | ACS Omega | - |
???dc.source???: dc.source | Scopus | - |
Título: dc.title | Design of a Helical-Stabilized, Cyclic, and Nontoxic Analogue of the Peptide Cm-p5 with Improved Antifungal Activity | - |
Tipo de arquivo: dc.type | livro digital | - |
Aparece nas coleções: | Repositório Institucional - Unesp |
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