Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR

Autores
Bortolus, Marco; Dalzini, Annalisa; Maniero, Anna Lisa; Panighel, Giacomo; Siano, Alvaro Sebastían; Toniolo, Claudio; De Zotti, Marta; Formaggio, Fernando
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Trichogin GA IV is a short-length (10-amino acid long), mostly hydrophobic, peptaibiotic with an N-terminal fatty acyl chain and a C-terminal 1,2-amino alcohol. A cardinal role of the terminal moieties in the cytotoxic activity of trichogin has been recently found. Previously, peptide orientation and dynamics of trichogin analogs in the membrane were studied using methyl ester derivatives. Therefore, in the present work we synthesized several trichogin analogs with naturally occurring terminal groups to verify whether these moieties have any effect on peptide-membrane interaction. These trichogin analogs, both neutral and carrying a positively charged Lys residue, bear the nitroxide-containing α-amino acid TOAC to study them using EPR spectroscopy. Vesicles were used to investigate orientation and penetration depth of the peptide at room temperature. Bicelles were employed to evaluate the order, dynamics, and orientation of the peptide at a near physiological temperature. In addition, the position of the N-terminal 1-octanoyl chain in the membrane was studied by labeling it with a nitroxide. The secondary structure of the peptides in vesicles was studied by CD spectroscopy showing that they adopt a mostly α-helical structure. In vesicles, the analogs insert below the lipid headgroups with the helix axis oriented parallel to the membrane surface at a peptide-to-lipid (P:L) ratio of 1:100. The presence of the single, positively charged Lys residue does not alter the orientation adopted by the peptides. In bicelles at P:L ratios 1:100 and 1:60, the peptide adopts a transmembrane orientation characterized by a very low orientational order, whereas at a 1:15 P:L ratio it severely disrupts the membrane. Our data shows that overall orientation and insertion in model membranes of the native trichogin GA IV are strictly comparable to those of its methyl ester analogs previously examined.
Fil: Bortolus, Marco. Università di Padova; Italia
Fil: Dalzini, Annalisa. Università di Padova; Italia
Fil: Maniero, Anna Lisa. Università di Padova; Italia
Fil: Panighel, Giacomo. Università di Padova; Italia
Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Università di Padova; Italia
Fil: Toniolo, Claudio. Università di Padova; Italia. Institute of Biomolecular Chemistry; Italia
Fil: De Zotti, Marta. Università di Padova; Italia
Fil: Formaggio, Fernando. Università di Padova; Italia. Institute of Biomolecular Chemistry; Italia
Materia
Bicelles
Circular Dichroism
Electron Paramagnetic Resonance
Membranes
Trichogin
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/66107
Acceder
id CONICETDig_b6abea1e7490fc78e0ff707cffcdd6a5
oai_identifier_str oai:ri.conicet.gov.ar:11336/66107
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPRBortolus, MarcoDalzini, AnnalisaManiero, Anna LisaPanighel, GiacomoSiano, Alvaro SebastíanToniolo, ClaudioDe Zotti, MartaFormaggio, FernandoBicellesCircular DichroismElectron Paramagnetic ResonanceMembranesTrichoginhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Trichogin GA IV is a short-length (10-amino acid long), mostly hydrophobic, peptaibiotic with an N-terminal fatty acyl chain and a C-terminal 1,2-amino alcohol. A cardinal role of the terminal moieties in the cytotoxic activity of trichogin has been recently found. Previously, peptide orientation and dynamics of trichogin analogs in the membrane were studied using methyl ester derivatives. Therefore, in the present work we synthesized several trichogin analogs with naturally occurring terminal groups to verify whether these moieties have any effect on peptide-membrane interaction. These trichogin analogs, both neutral and carrying a positively charged Lys residue, bear the nitroxide-containing α-amino acid TOAC to study them using EPR spectroscopy. Vesicles were used to investigate orientation and penetration depth of the peptide at room temperature. Bicelles were employed to evaluate the order, dynamics, and orientation of the peptide at a near physiological temperature. In addition, the position of the N-terminal 1-octanoyl chain in the membrane was studied by labeling it with a nitroxide. The secondary structure of the peptides in vesicles was studied by CD spectroscopy showing that they adopt a mostly α-helical structure. In vesicles, the analogs insert below the lipid headgroups with the helix axis oriented parallel to the membrane surface at a peptide-to-lipid (P:L) ratio of 1:100. The presence of the single, positively charged Lys residue does not alter the orientation adopted by the peptides. In bicelles at P:L ratios 1:100 and 1:60, the peptide adopts a transmembrane orientation characterized by a very low orientational order, whereas at a 1:15 P:L ratio it severely disrupts the membrane. Our data shows that overall orientation and insertion in model membranes of the native trichogin GA IV are strictly comparable to those of its methyl ester analogs previously examined.Fil: Bortolus, Marco. Università di Padova; ItaliaFil: Dalzini, Annalisa. Università di Padova; ItaliaFil: Maniero, Anna Lisa. Università di Padova; ItaliaFil: Panighel, Giacomo. Università di Padova; ItaliaFil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Università di Padova; ItaliaFil: Toniolo, Claudio. Università di Padova; Italia. Institute of Biomolecular Chemistry; ItaliaFil: De Zotti, Marta. Università di Padova; ItaliaFil: Formaggio, Fernando. Università di Padova; Italia. Institute of Biomolecular Chemistry; ItaliaJohn Wiley & Sons Inc2017-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66107Bortolus, Marco; Dalzini, Annalisa; Maniero, Anna Lisa; Panighel, Giacomo; Siano, Alvaro Sebastían; et al.; Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR; John Wiley & Sons Inc; Biopolymers; 108; 1; 1-2017; 1-130006-3525CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/bip.22913info:eu-repo/semantics/altIdentifier/doi/10.1002/bip.22913info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:09:04Zoai:ri.conicet.gov.ar:11336/66107instacron: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:34982025-09-10 13:09:05.208CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR
title Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR
spellingShingle Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR
Bortolus, Marco
Bicelles
Circular Dichroism
Electron Paramagnetic Resonance
Membranes
Trichogin
title_short Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR
title_full Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR
title_fullStr Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR
title_full_unstemmed Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR
title_sort Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR
dc.creator.none.fl_str_mv Bortolus, Marco
Dalzini, Annalisa
Maniero, Anna Lisa
Panighel, Giacomo
Siano, Alvaro Sebastían
Toniolo, Claudio
De Zotti, Marta
Formaggio, Fernando
author Bortolus, Marco
author_facet Bortolus, Marco
Dalzini, Annalisa
Maniero, Anna Lisa
Panighel, Giacomo
Siano, Alvaro Sebastían
Toniolo, Claudio
De Zotti, Marta
Formaggio, Fernando
author_role author
author2 Dalzini, Annalisa
Maniero, Anna Lisa
Panighel, Giacomo
Siano, Alvaro Sebastían
Toniolo, Claudio
De Zotti, Marta
Formaggio, Fernando
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bicelles
Circular Dichroism
Electron Paramagnetic Resonance
Membranes
Trichogin
topic Bicelles
Circular Dichroism
Electron Paramagnetic Resonance
Membranes
Trichogin
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trichogin GA IV is a short-length (10-amino acid long), mostly hydrophobic, peptaibiotic with an N-terminal fatty acyl chain and a C-terminal 1,2-amino alcohol. A cardinal role of the terminal moieties in the cytotoxic activity of trichogin has been recently found. Previously, peptide orientation and dynamics of trichogin analogs in the membrane were studied using methyl ester derivatives. Therefore, in the present work we synthesized several trichogin analogs with naturally occurring terminal groups to verify whether these moieties have any effect on peptide-membrane interaction. These trichogin analogs, both neutral and carrying a positively charged Lys residue, bear the nitroxide-containing α-amino acid TOAC to study them using EPR spectroscopy. Vesicles were used to investigate orientation and penetration depth of the peptide at room temperature. Bicelles were employed to evaluate the order, dynamics, and orientation of the peptide at a near physiological temperature. In addition, the position of the N-terminal 1-octanoyl chain in the membrane was studied by labeling it with a nitroxide. The secondary structure of the peptides in vesicles was studied by CD spectroscopy showing that they adopt a mostly α-helical structure. In vesicles, the analogs insert below the lipid headgroups with the helix axis oriented parallel to the membrane surface at a peptide-to-lipid (P:L) ratio of 1:100. The presence of the single, positively charged Lys residue does not alter the orientation adopted by the peptides. In bicelles at P:L ratios 1:100 and 1:60, the peptide adopts a transmembrane orientation characterized by a very low orientational order, whereas at a 1:15 P:L ratio it severely disrupts the membrane. Our data shows that overall orientation and insertion in model membranes of the native trichogin GA IV are strictly comparable to those of its methyl ester analogs previously examined.
Fil: Bortolus, Marco. Università di Padova; Italia
Fil: Dalzini, Annalisa. Università di Padova; Italia
Fil: Maniero, Anna Lisa. Università di Padova; Italia
Fil: Panighel, Giacomo. Università di Padova; Italia
Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Università di Padova; Italia
Fil: Toniolo, Claudio. Università di Padova; Italia. Institute of Biomolecular Chemistry; Italia
Fil: De Zotti, Marta. Università di Padova; Italia
Fil: Formaggio, Fernando. Università di Padova; Italia. Institute of Biomolecular Chemistry; Italia
description Trichogin GA IV is a short-length (10-amino acid long), mostly hydrophobic, peptaibiotic with an N-terminal fatty acyl chain and a C-terminal 1,2-amino alcohol. A cardinal role of the terminal moieties in the cytotoxic activity of trichogin has been recently found. Previously, peptide orientation and dynamics of trichogin analogs in the membrane were studied using methyl ester derivatives. Therefore, in the present work we synthesized several trichogin analogs with naturally occurring terminal groups to verify whether these moieties have any effect on peptide-membrane interaction. These trichogin analogs, both neutral and carrying a positively charged Lys residue, bear the nitroxide-containing α-amino acid TOAC to study them using EPR spectroscopy. Vesicles were used to investigate orientation and penetration depth of the peptide at room temperature. Bicelles were employed to evaluate the order, dynamics, and orientation of the peptide at a near physiological temperature. In addition, the position of the N-terminal 1-octanoyl chain in the membrane was studied by labeling it with a nitroxide. The secondary structure of the peptides in vesicles was studied by CD spectroscopy showing that they adopt a mostly α-helical structure. In vesicles, the analogs insert below the lipid headgroups with the helix axis oriented parallel to the membrane surface at a peptide-to-lipid (P:L) ratio of 1:100. The presence of the single, positively charged Lys residue does not alter the orientation adopted by the peptides. In bicelles at P:L ratios 1:100 and 1:60, the peptide adopts a transmembrane orientation characterized by a very low orientational order, whereas at a 1:15 P:L ratio it severely disrupts the membrane. Our data shows that overall orientation and insertion in model membranes of the native trichogin GA IV are strictly comparable to those of its methyl ester analogs previously examined.
publishDate 2017
dc.date.none.fl_str_mv 2017-01
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/11336/66107
Bortolus, Marco; Dalzini, Annalisa; Maniero, Anna Lisa; Panighel, Giacomo; Siano, Alvaro Sebastían; et al.; Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR; John Wiley & Sons Inc; Biopolymers; 108; 1; 1-2017; 1-13
0006-3525
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66107
identifier_str_mv Bortolus, Marco; Dalzini, Annalisa; Maniero, Anna Lisa; Panighel, Giacomo; Siano, Alvaro Sebastían; et al.; Insights into peptide-membrane interactions of newly synthesized, nitroxide-containing analogs of the peptaibiotic trichogin GA IV using EPR; John Wiley & Sons Inc; Biopolymers; 108; 1; 1-2017; 1-13
0006-3525
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/bip.22913
info:eu-repo/semantics/altIdentifier/doi/10.1002/bip.22913
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons Inc
publisher.none.fl_str_mv John Wiley & Sons Inc
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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score 12.993085

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