D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides
- Autores
- Húmpola, Maria Veronica; Spinelli, Roque; Erben, Melina; Perdomo, Virginia; Tonarelli, Georgina Guadalupe; Albericio, Fernando; Siano, Alvaro Sebastían
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic α-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, hydrophobicity, and critical micelle concentration, as well as their antimicrobial activity against gram-positive and gram-negative bacteria and yeast. Our results showed that substitution with D- and N-methyl amino acids could be a useful strategy to modulate the therapeutic properties of antimicrobial peptides and lipopeptides, including enhancing stability against enzymatic degradation. The study provides insights into the design and optimization of antimicrobial peptides to achieve improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies.
Fil: Húmpola, Maria Veronica. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Spinelli, Roque. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Erben, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina
Fil: Perdomo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Tonarelli, Georgina Guadalupe. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina
Fil: Albericio, Fernando. Instituto de Investigación Biomédica de Barcelona.; España
Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina - Materia
-
ANTIMICROBIAL PEPTIDES
D-AMINO ACIDS
ENZYMATIC STABILITY
N-METHYL AMINO ACIDS
TOXICITY - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/223198
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/223198 |
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D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and LipopeptidesHúmpola, Maria VeronicaSpinelli, RoqueErben, MelinaPerdomo, VirginiaTonarelli, Georgina GuadalupeAlbericio, FernandoSiano, Alvaro SebastíanANTIMICROBIAL PEPTIDESD-AMINO ACIDSENZYMATIC STABILITYN-METHYL AMINO ACIDSTOXICITYhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic α-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, hydrophobicity, and critical micelle concentration, as well as their antimicrobial activity against gram-positive and gram-negative bacteria and yeast. Our results showed that substitution with D- and N-methyl amino acids could be a useful strategy to modulate the therapeutic properties of antimicrobial peptides and lipopeptides, including enhancing stability against enzymatic degradation. The study provides insights into the design and optimization of antimicrobial peptides to achieve improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies.Fil: Húmpola, Maria Veronica. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Spinelli, Roque. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Erben, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; ArgentinaFil: Perdomo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Tonarelli, Georgina Guadalupe. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; ArgentinaFil: Albericio, Fernando. Instituto de Investigación Biomédica de Barcelona.; EspañaFil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2023-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/223198Húmpola, Maria Veronica; Spinelli, Roque; Erben, Melina; Perdomo, Virginia; Tonarelli, Georgina Guadalupe; et al.; D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides; MDPI; Antibiotics; 12; 5; 4-2023; 821-8372079-6382CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2079-6382/12/5/821info:eu-repo/semantics/altIdentifier/doi/10.3390/antibiotics12050821info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:30:52Zoai:ri.conicet.gov.ar:11336/223198instacron: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:34982025-09-29 10:30:52.438CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides |
title |
D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides |
spellingShingle |
D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides Húmpola, Maria Veronica ANTIMICROBIAL PEPTIDES D-AMINO ACIDS ENZYMATIC STABILITY N-METHYL AMINO ACIDS TOXICITY |
title_short |
D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides |
title_full |
D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides |
title_fullStr |
D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides |
title_full_unstemmed |
D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides |
title_sort |
D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides |
dc.creator.none.fl_str_mv |
Húmpola, Maria Veronica Spinelli, Roque Erben, Melina Perdomo, Virginia Tonarelli, Georgina Guadalupe Albericio, Fernando Siano, Alvaro Sebastían |
author |
Húmpola, Maria Veronica |
author_facet |
Húmpola, Maria Veronica Spinelli, Roque Erben, Melina Perdomo, Virginia Tonarelli, Georgina Guadalupe Albericio, Fernando Siano, Alvaro Sebastían |
author_role |
author |
author2 |
Spinelli, Roque Erben, Melina Perdomo, Virginia Tonarelli, Georgina Guadalupe Albericio, Fernando Siano, Alvaro Sebastían |
author2_role |
author author author author author author |
dc.subject.none.fl_str_mv |
ANTIMICROBIAL PEPTIDES D-AMINO ACIDS ENZYMATIC STABILITY N-METHYL AMINO ACIDS TOXICITY |
topic |
ANTIMICROBIAL PEPTIDES D-AMINO ACIDS ENZYMATIC STABILITY N-METHYL AMINO ACIDS TOXICITY |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic α-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, hydrophobicity, and critical micelle concentration, as well as their antimicrobial activity against gram-positive and gram-negative bacteria and yeast. Our results showed that substitution with D- and N-methyl amino acids could be a useful strategy to modulate the therapeutic properties of antimicrobial peptides and lipopeptides, including enhancing stability against enzymatic degradation. The study provides insights into the design and optimization of antimicrobial peptides to achieve improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies. Fil: Húmpola, Maria Veronica. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Spinelli, Roque. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Erben, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina Fil: Perdomo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Tonarelli, Georgina Guadalupe. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina Fil: Albericio, Fernando. Instituto de Investigación Biomédica de Barcelona.; España Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
description |
Here we designed and synthesized analogs of two antimicrobial peptides, namely C10:0-A2, a lipopeptide, and TA4, a cationic α-helical amphipathic peptide, and used non-proteinogenic amino acids to improve their therapeutic properties. The physicochemical properties of these analogs were analyzed, including their retention time, hydrophobicity, and critical micelle concentration, as well as their antimicrobial activity against gram-positive and gram-negative bacteria and yeast. Our results showed that substitution with D- and N-methyl amino acids could be a useful strategy to modulate the therapeutic properties of antimicrobial peptides and lipopeptides, including enhancing stability against enzymatic degradation. The study provides insights into the design and optimization of antimicrobial peptides to achieve improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-04 |
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/11336/223198 Húmpola, Maria Veronica; Spinelli, Roque; Erben, Melina; Perdomo, Virginia; Tonarelli, Georgina Guadalupe; et al.; D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides; MDPI; Antibiotics; 12; 5; 4-2023; 821-837 2079-6382 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/223198 |
identifier_str_mv |
Húmpola, Maria Veronica; Spinelli, Roque; Erben, Melina; Perdomo, Virginia; Tonarelli, Georgina Guadalupe; et al.; D- and N-Methyl Amino Acids for Modulating the Therapeutic Properties of Antimicrobial Peptides and Lipopeptides; MDPI; Antibiotics; 12; 5; 4-2023; 821-837 2079-6382 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/2079-6382/12/5/821 info:eu-repo/semantics/altIdentifier/doi/10.3390/antibiotics12050821 |
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 |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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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1844614317584941056 |
score |
13.070432 |