Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents

Over the last decades, multidrug-resistant bacteria have emerged and spread, increasing the number of bacteria, against which commonly used antibiotics are no longer effective. It has become a serious public health problem whose solution requires medical research in order to explore novel effective...

Descripción completa

Detalles Bibliográficos
Autores: Fernandez, Jael, Acosta, Gerardo A., Pulido, Daniel, Malý, Marek, Copa-Patiño, J.L., Royo, Miriam, Gómez, Rafael, Albericio, Fernando, Ortega, Paula, de la Mata, Javier
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/200824
Acceso en línea:http://hdl.handle.net/10261/200824
Access Level:acceso abierto
Palabra clave:Antibacterial peptides
Carbosilane dendrons
Molecular modeling and molecular dynamics
id ES_6cc79a5aed6e8616de36c8dbe1bff0b9
oai_identifier_str oai:digital.csic.es:10261/200824
network_acronym_str ES
network_name_str España
repository_id_str
spelling Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial AgentsFernandez, JaelAcosta, Gerardo A.Pulido, DanielMalý, MarekCopa-Patiño, J.L.Royo, MiriamGómez, RafaelAlbericio, FernandoOrtega, Paulade la Mata, JavierAntibacterial peptidesCarbosilane dendronsMolecular modeling and molecular dynamicsOver the last decades, multidrug-resistant bacteria have emerged and spread, increasing the number of bacteria, against which commonly used antibiotics are no longer effective. It has become a serious public health problem whose solution requires medical research in order to explore novel effective antimicrobial molecules. On the one hand, antimicrobial peptides (AMPs) are regarded as good alternatives because of their generally broad-spectrum activities, but sometimes they can be easily degraded by the organism or be toxic to animal cells. On the other hand, cationic carbosilane dendrons, whose focal point can be functionalized in many different ways, have also shown good antimicrobial activity. In this work, we synthetized first- and second-generation cationic carbosilane dendrons with a maleimide molecule on their focal point, enabling their functionalization with three different AMPs. After different microbiology studies, we found an additive effect between first-generation dendron and AMP3 whose study reveals three interesting effects: (i) bacteria aggregation due to AMP3, which could facilitate bacteria detection or even contribute to antibacterial activity by preventing host cell attack, (ii) bacteria disaggregation capability of second-generation cationic dendrons, and (iii) a higher AMP3 aggregation ability when dendrons were added previously to peptide treatment. These compounds and their different effects observed over bacteria constitute an interesting system for further mechanism studies. © 2019 American Chemical Society.This work has been supported by grants from CTQ2017-86224-P (MINECO), Consortiums NANODENDMED II-CM ref B2017/BMD-3703, and IMMUNOTHERCAN-CM B2017/BMD-3733 (CAM) to UAH. This study was funded by grants from the Spanish Ministerio de Economía, Industria y Competitividad (SAF2014-60138-R to M.R. those grants may include FEDER funds) and Generalitat de Catalunya (2017SGR1439). This work was also supported from ERDF/ESF project “UniQSurf—Centre of Biointerfaces and Hybrid Functional Materials” (no. CZ.02.1.01/0.0/0.0/17_048/0007411) and from the Research Infrastructure NanoEnviCz, supported by the Ministry of Education, Youth and Sports of the Czech Republic under project no. LM2015073. CIBER-BBN as an initiative funded by VI National R-D-i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. A.B. Acknown Ministerio de Economía y Competitividad for a predoctoral fellowship.Peer reviewedAmerican Chemical SocietyMinisterio de Economía y Competitividad (España)Royo, Miriam [0000-0001-5292-0819]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/200824reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-60138-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2017-86224-Phttps://doi.org/10.1021/acs.molpharmaceut.9b00222Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2008242026-05-22T06:33:51Z
dc.title.none.fl_str_mv Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents
title Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents
spellingShingle Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents
Fernandez, Jael
Antibacterial peptides
Carbosilane dendrons
Molecular modeling and molecular dynamics
title_short Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents
title_full Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents
title_fullStr Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents
title_full_unstemmed Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents
title_sort Carbosilane Dendron–Peptide Nanoconjugates as Antimicrobial Agents
dc.creator.none.fl_str_mv Fernandez, Jael
Acosta, Gerardo A.
Pulido, Daniel
Malý, Marek
Copa-Patiño, J.L.
Royo, Miriam
Gómez, Rafael
Albericio, Fernando
Ortega, Paula
de la Mata, Javier
author Fernandez, Jael
author_facet Fernandez, Jael
Acosta, Gerardo A.
Pulido, Daniel
Malý, Marek
Copa-Patiño, J.L.
Royo, Miriam
Gómez, Rafael
Albericio, Fernando
Ortega, Paula
de la Mata, Javier
author_role author
author2 Acosta, Gerardo A.
Pulido, Daniel
Malý, Marek
Copa-Patiño, J.L.
Royo, Miriam
Gómez, Rafael
Albericio, Fernando
Ortega, Paula
de la Mata, Javier
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Royo, Miriam [0000-0001-5292-0819]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Antibacterial peptides
Carbosilane dendrons
Molecular modeling and molecular dynamics
topic Antibacterial peptides
Carbosilane dendrons
Molecular modeling and molecular dynamics
description Over the last decades, multidrug-resistant bacteria have emerged and spread, increasing the number of bacteria, against which commonly used antibiotics are no longer effective. It has become a serious public health problem whose solution requires medical research in order to explore novel effective antimicrobial molecules. On the one hand, antimicrobial peptides (AMPs) are regarded as good alternatives because of their generally broad-spectrum activities, but sometimes they can be easily degraded by the organism or be toxic to animal cells. On the other hand, cationic carbosilane dendrons, whose focal point can be functionalized in many different ways, have also shown good antimicrobial activity. In this work, we synthetized first- and second-generation cationic carbosilane dendrons with a maleimide molecule on their focal point, enabling their functionalization with three different AMPs. After different microbiology studies, we found an additive effect between first-generation dendron and AMP3 whose study reveals three interesting effects: (i) bacteria aggregation due to AMP3, which could facilitate bacteria detection or even contribute to antibacterial activity by preventing host cell attack, (ii) bacteria disaggregation capability of second-generation cationic dendrons, and (iii) a higher AMP3 aggregation ability when dendrons were added previously to peptide treatment. These compounds and their different effects observed over bacteria constitute an interesting system for further mechanism studies. © 2019 American Chemical Society.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/200824
url http://hdl.handle.net/10261/200824
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-60138-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2017-86224-P
https://doi.org/10.1021/acs.molpharmaceut.9b00222
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410292670136321
score 15,198674

Similares en LA Referencia