Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies

Detalhes bibliográficos
Autor(a) principal: Domingues, Marco M.
Data de Publicação: 2012
Outros Autores: Santos, Nuno C., Castanho, Miguel A. R. B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/10763
Resumo: © 2012 Bentham Science Publishers
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spelling Antimicrobial peptide rBPI21: a translational overview from bench to clinical studiesrBPI21LipopolysaccharideMicrobicideMembranesClinical trials© 2012 Bentham Science PublishersGram-negative bacteria infection is sometimes followed by septic shock. This serious health condition is caused by the segregation of the lipopolysaccharide (LPS) from bacterial membrane into the bloodstream. Due to bacterial resistance, new antibiotics are needed. Most of the active antibiotics possess bactericidal effect, but lack LPS neutralization properties to prevent or neutralize septic shock. Antimicrobial peptides are a new class of antibiotics not prone to bacterial resistance, because their main target is the membrane. It is difficult for bacteria to critically change their membrane composition without affecting its molecular processes. rBPI21 is a recombinant antimicrobial peptide developed from an antimicrobial protein produced in neutrophils, the bactericidal/permeability-increasing protein (BPI) that ended phase III clinical trials against meningitis with success, reducing serious complications, such as amputations. It interacts preferentially with LPS with high affinity and at the same time has bactericidal effect. Here, we gather evidence that the interaction of the rBPI21 with LPS is mainly electrostatic, first, followed by massive LPS aggregation, which is correlated with its clearance from the bloodstream. The molecular mechanism at membrane level includes the peptide interactions with negatively charged phospholipids that promote outer and inner membrane hemi(fusion). This perturbation is followed by membrane permeabilization.This work was partially funded by Fundação para a Ciência e a Tecnologia of the Ministério da Educação Ciência, Tecnologia e Ensino Superior (FCT-MEC, Portugal). MMD also acknowledges FCT-MEC for fellowship SFRH/BD/41750/2007.Bentham Science PublishersRepositório da Universidade de LisboaDomingues, Marco M.Santos, Nuno C.Castanho, Miguel A. R. B.2014-03-21T11:06:03Z20122012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/10763engCurrent Protein and Peptide Science, 2012, 13, 611-6191389-2037http://dx.doi.org/10.2174/138920312804142101metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:56:28Zoai:repositorio.ul.pt:10451/10763Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:34:40.933386Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies
title Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies
spellingShingle Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies
Domingues, Marco M.
rBPI21
Lipopolysaccharide
Microbicide
Membranes
Clinical trials
title_short Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies
title_full Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies
title_fullStr Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies
title_full_unstemmed Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies
title_sort Antimicrobial peptide rBPI21: a translational overview from bench to clinical studies
author Domingues, Marco M.
author_facet Domingues, Marco M.
Santos, Nuno C.
Castanho, Miguel A. R. B.
author_role author
author2 Santos, Nuno C.
Castanho, Miguel A. R. B.
author2_role author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Domingues, Marco M.
Santos, Nuno C.
Castanho, Miguel A. R. B.
dc.subject.por.fl_str_mv rBPI21
Lipopolysaccharide
Microbicide
Membranes
Clinical trials
topic rBPI21
Lipopolysaccharide
Microbicide
Membranes
Clinical trials
description © 2012 Bentham Science Publishers
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-01-01T00:00:00Z
2014-03-21T11:06:03Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/10763
url http://hdl.handle.net/10451/10763
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Current Protein and Peptide Science, 2012, 13, 611-619
1389-2037
http://dx.doi.org/10.2174/138920312804142101
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dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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