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Amino acids
Jan, 2023;55 (1): 113-124.

Inspiration from cruzioseptin-1: membranolytic analogue with improved antibacterial properties.

Sebastián Bermúdez-Puga, Giovanna Morán-Marcillo, Nina Espinosa de Los Monteros-Silva, Renato E Naranjo, Fernanda Toscano, Karla Vizuete, Marbel Torres Arias, José R Almeida, Carolina Proaño-Bolaños
Author Information
  1. Sebastián Bermúdez-Puga: Biomolecules Discovery Group, Laboratory of Molecular Biology and Biochemistry, Universidad Regional Amazónica Ikiam, Km 7 ½ Vía Muyuna, Tena, Napo, 150150, Ecuador.
  2. Giovanna Morán-Marcillo: Biomolecules Discovery Group, Laboratory of Molecular Biology and Biochemistry, Universidad Regional Amazónica Ikiam, Km 7 ½ Vía Muyuna, Tena, Napo, 150150, Ecuador.
  3. Nina Espinosa de Los Monteros-Silva: Biomolecules Discovery Group, Laboratory of Molecular Biology and Biochemistry, Universidad Regional Amazónica Ikiam, Km 7 ½ Vía Muyuna, Tena, Napo, 150150, Ecuador.
  4. Renato E Naranjo: Dirección Nacional de Biodiversidad, Ministerio del Ambiente, Agua y Transición Ecológica, Madrid 1159 y Andalucía, Quito, 170525, Ecuador.
  5. Fernanda Toscano: Departamento de Ciencias de la Vida y Agricultura, Laboratorio de Inmunología y Virología, Universidad de las Fuerzas Armadas ESPE, CENCINAT, GISAH Av. Gral. Rumiñahui S/N, P.O. Box 171, -5-231B, Sangolquí, Ecuador.
  6. Karla Vizuete: Center of Nanoscience and Nanotechnology, Universidad de las Fuerzas Armadas ESPE, Sangolquí, 170501, Ecuador.
  7. Marbel Torres Arias: Departamento de Ciencias de la Vida y Agricultura, Laboratorio de Inmunología y Virología, Universidad de las Fuerzas Armadas ESPE, CENCINAT, GISAH Av. Gral. Rumiñahui S/N, P.O. Box 171, -5-231B, Sangolquí, Ecuador.
  8. José R Almeida: Biomolecules Discovery Group, Laboratory of Molecular Biology and Biochemistry, Universidad Regional Amazónica Ikiam, Km 7 ½ Vía Muyuna, Tena, Napo, 150150, Ecuador.
  9. Carolina Proaño-Bolaños: Biomolecules Discovery Group, Laboratory of Molecular Biology and Biochemistry, Universidad Regional Amazónica Ikiam, Km 7 ½ Vía Muyuna, Tena, Napo, 150150, Ecuador. carolina.proano@ikiam.edu.ec. ORCID
PMID: 36609571 DOI: 10.1007/s00726-022-03209-6

Abstract

Peptide engineering has gained attraction as a source of new cationicity-enhanced analogues with high potential for the design of next-generation antibiotics. In this context, cruzioseptin-1 (CZS-1), a peptide identified from Cruziohyla calcarifer, is recognized for its antimicrobial potency. However, this amidated-peptide is moderately hemolytic. In order to reduce toxicity and increase antimicrobial potency, 3 peptide analogues based on cruzioseptin-1 were designed and evaluated. [K4K15]CZS-1, an analogue with increased cationicity and reduced hydrophobicity, showed antibacterial, antifungal and antiproliferative properties. In addition, [K4K15]CZS-1 is less hemolytic than CZS-1. The in silico and scanning electron microscopy analysis reveal that [K4K15]CZS-1 induces a membranolytic effect on bacteria. Overall, these results confirm the potential of CZS-1 as source of inspiration for design new selective antimicrobial analogues useful for development of new therapeutic agents.

Keywords

Antimicrobial peptides Cruzioseptin Membranolytic effect Rational design

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Grants

  1. GEF ID 5534/Global Environment Facility

MeSH Term

Antimicrobial Cationic Peptides
Amino Acid Sequence
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Microbial Sensitivity Tests

Chemicals

Antimicrobial Cationic Peptides
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Journal Article
Article has an altmetric score of 9

Word Cloud

Created with Highcharts 10.0.0newanaloguesdesignCZS-1antimicrobial[K4K15]CZS-1sourcepotentialcruzioseptin-1peptidepotencyhemolyticanalogueantibacterialpropertiesmembranolyticeffectPeptideengineeringgainedattractioncationicity-enhancedhighnext-generationantibioticscontextidentifiedCruziohylacalcariferrecognizedHoweveramidated-peptidemoderatelyorderreducetoxicityincrease3baseddesignedevaluatedincreasedcationicityreducedhydrophobicityshowedantifungalantiproliferativeadditionlesssilicoscanningelectronmicroscopyanalysisrevealinducesbacteriaOverallresultsconfirminspirationselectiveusefuldevelopmenttherapeuticagentsInspirationcruzioseptin-1:improvedAntimicrobialpeptidesCruzioseptinMembranolyticRational

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