Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
- Autores
- Heinrich, Frank; Salyapongse, Aria; Kumagai, Akari; Dupuy, Fernando Gabriel; Shukla, Karpur; Penk, Anja; Huster, Daniel; Ernst, Robert K.; Pavlova, Anna; Gumbart, James C.; Deslouches, Berthony; Di, Y. Peter; Tristram-Nagle, Stephanie
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.
Fil: Heinrich, Frank. University of Carnegie Mellon; Estados Unidos
Fil: Salyapongse, Aria. University of Carnegie Mellon; Estados Unidos
Fil: Kumagai, Akari. University of Carnegie Mellon; Estados Unidos
Fil: Dupuy, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Shukla, Karpur. University of Carnegie Mellon; Estados Unidos
Fil: Penk, Anja. Universitat Leipzig; Alemania
Fil: Huster, Daniel. Universitat Leipzig; Alemania
Fil: Ernst, Robert K.. University of Maryland; Estados Unidos
Fil: Pavlova, Anna. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados Unidos
Fil: Gumbart, James C.. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados Unidos
Fil: Deslouches, Berthony. University of Pittsburgh; Estados Unidos
Fil: Di, Y. Peter. University of Pittsburgh; Estados Unidos
Fil: Tristram-Nagle, Stephanie. University of Carnegie Mellon; Estados Unidos - Materia
-
DRUG DESIGN
ENGINEERED CATIONIC ANTIMICROBIAL PEPTIDES
MEMBRANES
NEUTRON REFLECTIVITY
PROTEIN–LIPID INTERACTIONS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/184335
Ver los metadatos del registro completo
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Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model MembranesHeinrich, FrankSalyapongse, AriaKumagai, AkariDupuy, Fernando GabrielShukla, KarpurPenk, AnjaHuster, DanielErnst, Robert K.Pavlova, AnnaGumbart, James C.Deslouches, BerthonyDi, Y. PeterTristram-Nagle, StephanieDRUG DESIGNENGINEERED CATIONIC ANTIMICROBIAL PEPTIDESMEMBRANESNEUTRON REFLECTIVITYPROTEIN–LIPID INTERACTIONShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.Fil: Heinrich, Frank. University of Carnegie Mellon; Estados UnidosFil: Salyapongse, Aria. University of Carnegie Mellon; Estados UnidosFil: Kumagai, Akari. University of Carnegie Mellon; Estados UnidosFil: Dupuy, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Shukla, Karpur. University of Carnegie Mellon; Estados UnidosFil: Penk, Anja. Universitat Leipzig; AlemaniaFil: Huster, Daniel. Universitat Leipzig; AlemaniaFil: Ernst, Robert K.. University of Maryland; Estados UnidosFil: Pavlova, Anna. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados UnidosFil: Gumbart, James C.. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados UnidosFil: Deslouches, Berthony. University of Pittsburgh; Estados UnidosFil: Di, Y. Peter. University of Pittsburgh; Estados UnidosFil: Tristram-Nagle, Stephanie. University of Carnegie Mellon; Estados UnidosWiley VCH Verlag2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/184335Heinrich, Frank; Salyapongse, Aria; Kumagai, Akari; Dupuy, Fernando Gabriel; Shukla, Karpur; et al.; Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes; Wiley VCH Verlag; Chemistry- A European Journal; 26; 28; 5-2020; 6247-62560947-6539CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202000212info:eu-repo/semantics/altIdentifier/doi/10.1002/chem.202000212info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:10:47Zoai:ri.conicet.gov.ar:11336/184335instacron: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:34982025-10-22 12:10:47.437CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes |
title |
Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes |
spellingShingle |
Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes Heinrich, Frank DRUG DESIGN ENGINEERED CATIONIC ANTIMICROBIAL PEPTIDES MEMBRANES NEUTRON REFLECTIVITY PROTEIN–LIPID INTERACTIONS |
title_short |
Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes |
title_full |
Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes |
title_fullStr |
Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes |
title_full_unstemmed |
Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes |
title_sort |
Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes |
dc.creator.none.fl_str_mv |
Heinrich, Frank Salyapongse, Aria Kumagai, Akari Dupuy, Fernando Gabriel Shukla, Karpur Penk, Anja Huster, Daniel Ernst, Robert K. Pavlova, Anna Gumbart, James C. Deslouches, Berthony Di, Y. Peter Tristram-Nagle, Stephanie |
author |
Heinrich, Frank |
author_facet |
Heinrich, Frank Salyapongse, Aria Kumagai, Akari Dupuy, Fernando Gabriel Shukla, Karpur Penk, Anja Huster, Daniel Ernst, Robert K. Pavlova, Anna Gumbart, James C. Deslouches, Berthony Di, Y. Peter Tristram-Nagle, Stephanie |
author_role |
author |
author2 |
Salyapongse, Aria Kumagai, Akari Dupuy, Fernando Gabriel Shukla, Karpur Penk, Anja Huster, Daniel Ernst, Robert K. Pavlova, Anna Gumbart, James C. Deslouches, Berthony Di, Y. Peter Tristram-Nagle, Stephanie |
author2_role |
author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
DRUG DESIGN ENGINEERED CATIONIC ANTIMICROBIAL PEPTIDES MEMBRANES NEUTRON REFLECTIVITY PROTEIN–LIPID INTERACTIONS |
topic |
DRUG DESIGN ENGINEERED CATIONIC ANTIMICROBIAL PEPTIDES MEMBRANES NEUTRON REFLECTIVITY PROTEIN–LIPID INTERACTIONS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8. Fil: Heinrich, Frank. University of Carnegie Mellon; Estados Unidos Fil: Salyapongse, Aria. University of Carnegie Mellon; Estados Unidos Fil: Kumagai, Akari. University of Carnegie Mellon; Estados Unidos Fil: Dupuy, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina Fil: Shukla, Karpur. University of Carnegie Mellon; Estados Unidos Fil: Penk, Anja. Universitat Leipzig; Alemania Fil: Huster, Daniel. Universitat Leipzig; Alemania Fil: Ernst, Robert K.. University of Maryland; Estados Unidos Fil: Pavlova, Anna. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados Unidos Fil: Gumbart, James C.. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados Unidos Fil: Deslouches, Berthony. University of Pittsburgh; Estados Unidos Fil: Di, Y. Peter. University of Pittsburgh; Estados Unidos Fil: Tristram-Nagle, Stephanie. University of Carnegie Mellon; Estados Unidos |
description |
In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-05 |
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/11336/184335 Heinrich, Frank; Salyapongse, Aria; Kumagai, Akari; Dupuy, Fernando Gabriel; Shukla, Karpur; et al.; Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes; Wiley VCH Verlag; Chemistry- A European Journal; 26; 28; 5-2020; 6247-6256 0947-6539 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/184335 |
identifier_str_mv |
Heinrich, Frank; Salyapongse, Aria; Kumagai, Akari; Dupuy, Fernando Gabriel; Shukla, Karpur; et al.; Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes; Wiley VCH Verlag; Chemistry- A European Journal; 26; 28; 5-2020; 6247-6256 0947-6539 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://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202000212 info:eu-repo/semantics/altIdentifier/doi/10.1002/chem.202000212 |
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 |
Wiley VCH Verlag |
publisher.none.fl_str_mv |
Wiley VCH Verlag |
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 |
_version_ |
1846782495587041280 |
score |
12.982451 |