Enhancing antimicrobial peptides from frog skin: A rational approach

Autores
Aguilar, Silvana; Moreira, Daniela; Pereira Lourenço, Ana Laura; Wilke, Natalia; Crosio, Matias Ariel; Vasconcelos, Andreanne; Alves Barbosa, Eder; Bispo, Elizabete C. I.; Saldanha Araujo, Felipe; Ramada, Marcelo H. S.; Escobar, Franco Matias; Torres, Cristina Vanesa; Leite, José R. S. A.; Marani, Mariela Mirta
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Antimicrobial resistance is a global health threat, which has been worsened by the slow development of new antibiotics. The rational design of natural-derived antimicrobial peptides (AMPs) offers a promising alternative for enhancing the efficacy of AMPs and accelerating drug discovery. This paper describes the rational design of improved peptide derivatives starting from hylin-Pul3, a peptide previously isolated from the frog Boana pulchella, by optimizing its hydrophobicity, cationicity, and amphipathicity. In silico screening identified six promising candidates: dHP3-31, dHP3-50, dHP3-50.137, dHP3-50.190, dHP3-84, and dHP3-84.39. These derivatives exhibited enhanced activity against Gram-negative bacteria, emphasizing the role of cationicity and the strategic arginine incorporation. Hemolytic assays revealed the derivatives’ improved selectivity, particularly for the derivatives with “imperfect amphipathicity”. In fibroblast assays, dHP3-84 was well-tolerated, while dHP3-84.39 promoted cell proliferation. Antioxidant assays (ABTS assays) highlighted the Trp-containing derivatives’ (dHP3-50.137, dHP3-31) significant activity. The lipid membrane interaction studies showed that hylin-Pul3 disrupts membranes directly, while dHP3-84.39, dHP3-50, and dHP3-50.137 promote vesicle aggregation. Conversely, dHP3-84 did not induce membrane disruption or aggregation, suggesting an intracellular mode of action. Machine learning models were effective in predicting bioactivity, as these predicted AMPs showed enhanced selectivity and potency. Among them, dHP3-84 demonstrated broad-spectrum potential. These findings highlight the value of rational design, in silico screening, and structure–activity studies in optimizing AMPs for therapeutic applications.
Fil: Aguilar, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina
Fil: Moreira, Daniela. Universidade do Brasília; Brasil
Fil: Pereira Lourenço, Ana Laura. Universidade Católica de Brasília; Brasil
Fil: Wilke, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina
Fil: Crosio, Matias Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina
Fil: Vasconcelos, Andreanne. Universidade do Brasília; Brasil. University Center of the Federal District; Brasil
Fil: Alves Barbosa, Eder. Universidade do Brasília; Brasil
Fil: Bispo, Elizabete C. I.. Universidade do Brasília; Brasil
Fil: Saldanha Araujo, Felipe. Universidade do Brasília; Brasil
Fil: Ramada, Marcelo H. S.. Universidade Católica de Brasília; Brasil
Fil: Escobar, Franco Matias. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina
Fil: Torres, Cristina Vanesa. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina
Fil: Leite, José R. S. A.. Universidade do Brasília; Brasil
Fil: Marani, Mariela Mirta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina
Materia
HYLINS
IN SILICO DESIGN
AMPHIPATHIC
PEPTIDE MEMBRANE INTERACTIONS
CELL SELECTIVITY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/289200
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Enhancing antimicrobial peptides from frog skin: A rational approachAguilar, SilvanaMoreira, DanielaPereira Lourenço, Ana LauraWilke, NataliaCrosio, Matias ArielVasconcelos, AndreanneAlves Barbosa, EderBispo, Elizabete C. I.Saldanha Araujo, FelipeRamada, Marcelo H. S.Escobar, Franco MatiasTorres, Cristina VanesaLeite, José R. S. A.Marani, Mariela MirtaHYLINSIN SILICO DESIGNAMPHIPATHICPEPTIDE MEMBRANE INTERACTIONSCELL SELECTIVITYhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Antimicrobial resistance is a global health threat, which has been worsened by the slow development of new antibiotics. The rational design of natural-derived antimicrobial peptides (AMPs) offers a promising alternative for enhancing the efficacy of AMPs and accelerating drug discovery. This paper describes the rational design of improved peptide derivatives starting from hylin-Pul3, a peptide previously isolated from the frog Boana pulchella, by optimizing its hydrophobicity, cationicity, and amphipathicity. In silico screening identified six promising candidates: dHP3-31, dHP3-50, dHP3-50.137, dHP3-50.190, dHP3-84, and dHP3-84.39. These derivatives exhibited enhanced activity against Gram-negative bacteria, emphasizing the role of cationicity and the strategic arginine incorporation. Hemolytic assays revealed the derivatives’ improved selectivity, particularly for the derivatives with “imperfect amphipathicity”. In fibroblast assays, dHP3-84 was well-tolerated, while dHP3-84.39 promoted cell proliferation. Antioxidant assays (ABTS assays) highlighted the Trp-containing derivatives’ (dHP3-50.137, dHP3-31) significant activity. The lipid membrane interaction studies showed that hylin-Pul3 disrupts membranes directly, while dHP3-84.39, dHP3-50, and dHP3-50.137 promote vesicle aggregation. Conversely, dHP3-84 did not induce membrane disruption or aggregation, suggesting an intracellular mode of action. Machine learning models were effective in predicting bioactivity, as these predicted AMPs showed enhanced selectivity and potency. Among them, dHP3-84 demonstrated broad-spectrum potential. These findings highlight the value of rational design, in silico screening, and structure–activity studies in optimizing AMPs for therapeutic applications.Fil: Aguilar, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Moreira, Daniela. Universidade do Brasília; BrasilFil: Pereira Lourenço, Ana Laura. Universidade Católica de Brasília; BrasilFil: Wilke, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; ArgentinaFil: Crosio, Matias Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; ArgentinaFil: Vasconcelos, Andreanne. Universidade do Brasília; Brasil. University Center of the Federal District; BrasilFil: Alves Barbosa, Eder. Universidade do Brasília; BrasilFil: Bispo, Elizabete C. I.. Universidade do Brasília; BrasilFil: Saldanha Araujo, Felipe. Universidade do Brasília; BrasilFil: Ramada, Marcelo H. S.. Universidade Católica de Brasília; BrasilFil: Escobar, Franco Matias. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; ArgentinaFil: Torres, Cristina Vanesa. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; ArgentinaFil: Leite, José R. S. A.. Universidade do Brasília; BrasilFil: Marani, Mariela Mirta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaMultidisciplinary Digital Publishing Institute2025-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/289200Aguilar, Silvana; Moreira, Daniela; Pereira Lourenço, Ana Laura; Wilke, Natalia; Crosio, Matias Ariel; et al.; Enhancing antimicrobial peptides from frog skin: A rational approach; Multidisciplinary Digital Publishing Institute; Biomolecules; 15; 3; 3-2025; 1-222218-273XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2218-273X/15/3/449info:eu-repo/semantics/altIdentifier/doi/10.3390/biom15030449info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:33:14Zoai:ri.conicet.gov.ar:11336/289200instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 14:33:14.548CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Enhancing antimicrobial peptides from frog skin: A rational approach
title Enhancing antimicrobial peptides from frog skin: A rational approach
spellingShingle Enhancing antimicrobial peptides from frog skin: A rational approach
Aguilar, Silvana
HYLINS
IN SILICO DESIGN
AMPHIPATHIC
PEPTIDE MEMBRANE INTERACTIONS
CELL SELECTIVITY
title_short Enhancing antimicrobial peptides from frog skin: A rational approach
title_full Enhancing antimicrobial peptides from frog skin: A rational approach
title_fullStr Enhancing antimicrobial peptides from frog skin: A rational approach
title_full_unstemmed Enhancing antimicrobial peptides from frog skin: A rational approach
title_sort Enhancing antimicrobial peptides from frog skin: A rational approach
dc.creator.none.fl_str_mv Aguilar, Silvana
Moreira, Daniela
Pereira Lourenço, Ana Laura
Wilke, Natalia
Crosio, Matias Ariel
Vasconcelos, Andreanne
Alves Barbosa, Eder
Bispo, Elizabete C. I.
Saldanha Araujo, Felipe
Ramada, Marcelo H. S.
Escobar, Franco Matias
Torres, Cristina Vanesa
Leite, José R. S. A.
Marani, Mariela Mirta
author Aguilar, Silvana
author_facet Aguilar, Silvana
Moreira, Daniela
Pereira Lourenço, Ana Laura
Wilke, Natalia
Crosio, Matias Ariel
Vasconcelos, Andreanne
Alves Barbosa, Eder
Bispo, Elizabete C. I.
Saldanha Araujo, Felipe
Ramada, Marcelo H. S.
Escobar, Franco Matias
Torres, Cristina Vanesa
Leite, José R. S. A.
Marani, Mariela Mirta
author_role author
author2 Moreira, Daniela
Pereira Lourenço, Ana Laura
Wilke, Natalia
Crosio, Matias Ariel
Vasconcelos, Andreanne
Alves Barbosa, Eder
Bispo, Elizabete C. I.
Saldanha Araujo, Felipe
Ramada, Marcelo H. S.
Escobar, Franco Matias
Torres, Cristina Vanesa
Leite, José R. S. A.
Marani, Mariela Mirta
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HYLINS
IN SILICO DESIGN
AMPHIPATHIC
PEPTIDE MEMBRANE INTERACTIONS
CELL SELECTIVITY
topic HYLINS
IN SILICO DESIGN
AMPHIPATHIC
PEPTIDE MEMBRANE INTERACTIONS
CELL SELECTIVITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Antimicrobial resistance is a global health threat, which has been worsened by the slow development of new antibiotics. The rational design of natural-derived antimicrobial peptides (AMPs) offers a promising alternative for enhancing the efficacy of AMPs and accelerating drug discovery. This paper describes the rational design of improved peptide derivatives starting from hylin-Pul3, a peptide previously isolated from the frog Boana pulchella, by optimizing its hydrophobicity, cationicity, and amphipathicity. In silico screening identified six promising candidates: dHP3-31, dHP3-50, dHP3-50.137, dHP3-50.190, dHP3-84, and dHP3-84.39. These derivatives exhibited enhanced activity against Gram-negative bacteria, emphasizing the role of cationicity and the strategic arginine incorporation. Hemolytic assays revealed the derivatives’ improved selectivity, particularly for the derivatives with “imperfect amphipathicity”. In fibroblast assays, dHP3-84 was well-tolerated, while dHP3-84.39 promoted cell proliferation. Antioxidant assays (ABTS assays) highlighted the Trp-containing derivatives’ (dHP3-50.137, dHP3-31) significant activity. The lipid membrane interaction studies showed that hylin-Pul3 disrupts membranes directly, while dHP3-84.39, dHP3-50, and dHP3-50.137 promote vesicle aggregation. Conversely, dHP3-84 did not induce membrane disruption or aggregation, suggesting an intracellular mode of action. Machine learning models were effective in predicting bioactivity, as these predicted AMPs showed enhanced selectivity and potency. Among them, dHP3-84 demonstrated broad-spectrum potential. These findings highlight the value of rational design, in silico screening, and structure–activity studies in optimizing AMPs for therapeutic applications.
Fil: Aguilar, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina
Fil: Moreira, Daniela. Universidade do Brasília; Brasil
Fil: Pereira Lourenço, Ana Laura. Universidade Católica de Brasília; Brasil
Fil: Wilke, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina
Fil: Crosio, Matias Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Biológica; Argentina
Fil: Vasconcelos, Andreanne. Universidade do Brasília; Brasil. University Center of the Federal District; Brasil
Fil: Alves Barbosa, Eder. Universidade do Brasília; Brasil
Fil: Bispo, Elizabete C. I.. Universidade do Brasília; Brasil
Fil: Saldanha Araujo, Felipe. Universidade do Brasília; Brasil
Fil: Ramada, Marcelo H. S.. Universidade Católica de Brasília; Brasil
Fil: Escobar, Franco Matias. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina
Fil: Torres, Cristina Vanesa. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Fisicoquímicas y Naturales. Departamento de Microbiología e Inmunología; Argentina
Fil: Leite, José R. S. A.. Universidade do Brasília; Brasil
Fil: Marani, Mariela Mirta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina
description Antimicrobial resistance is a global health threat, which has been worsened by the slow development of new antibiotics. The rational design of natural-derived antimicrobial peptides (AMPs) offers a promising alternative for enhancing the efficacy of AMPs and accelerating drug discovery. This paper describes the rational design of improved peptide derivatives starting from hylin-Pul3, a peptide previously isolated from the frog Boana pulchella, by optimizing its hydrophobicity, cationicity, and amphipathicity. In silico screening identified six promising candidates: dHP3-31, dHP3-50, dHP3-50.137, dHP3-50.190, dHP3-84, and dHP3-84.39. These derivatives exhibited enhanced activity against Gram-negative bacteria, emphasizing the role of cationicity and the strategic arginine incorporation. Hemolytic assays revealed the derivatives’ improved selectivity, particularly for the derivatives with “imperfect amphipathicity”. In fibroblast assays, dHP3-84 was well-tolerated, while dHP3-84.39 promoted cell proliferation. Antioxidant assays (ABTS assays) highlighted the Trp-containing derivatives’ (dHP3-50.137, dHP3-31) significant activity. The lipid membrane interaction studies showed that hylin-Pul3 disrupts membranes directly, while dHP3-84.39, dHP3-50, and dHP3-50.137 promote vesicle aggregation. Conversely, dHP3-84 did not induce membrane disruption or aggregation, suggesting an intracellular mode of action. Machine learning models were effective in predicting bioactivity, as these predicted AMPs showed enhanced selectivity and potency. Among them, dHP3-84 demonstrated broad-spectrum potential. These findings highlight the value of rational design, in silico screening, and structure–activity studies in optimizing AMPs for therapeutic applications.
publishDate 2025
dc.date.none.fl_str_mv 2025-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/289200
Aguilar, Silvana; Moreira, Daniela; Pereira Lourenço, Ana Laura; Wilke, Natalia; Crosio, Matias Ariel; et al.; Enhancing antimicrobial peptides from frog skin: A rational approach; Multidisciplinary Digital Publishing Institute; Biomolecules; 15; 3; 3-2025; 1-22
2218-273X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/289200
identifier_str_mv Aguilar, Silvana; Moreira, Daniela; Pereira Lourenço, Ana Laura; Wilke, Natalia; Crosio, Matias Ariel; et al.; Enhancing antimicrobial peptides from frog skin: A rational approach; Multidisciplinary Digital Publishing Institute; Biomolecules; 15; 3; 3-2025; 1-22
2218-273X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2218-273X/15/3/449
info:eu-repo/semantics/altIdentifier/doi/10.3390/biom15030449
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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