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Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides

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Resumo:Motivation: The need for more effective and safer pharmaceuticals is a persistent quest. Microbial adaptations create the need to permanently develop new antimicrobials, for instance. Similarly, intracellular delivery of drugs is still a challenge and translocation of membranes for drug delivery is an area of intense research. Peptides can be used both as antimicrobial drug leads and drug carrier systems for intracellular delivery. Multifunctional proteins are abundant in viruses but, surprisingly, have never been thoroughly screened for bioactive peptide sequences. Results: Using the AMPA and CellPPD online tools we have evaluated the propensity of viral proteins to comprise antimicrobial (AMP) or cell-penetrating peptides (CPP). Capsid proteins from both enveloped and non-enveloped viruses, and membrane and envelope proteins from enveloped viruses, in a total of 272 proteins from 133 viruses, were screened to detect the presence of potential AMP and CPP sequences. A pool of 2444 and 426 CPP and AMP sequences, respectively, were discovered. The capsids of flaviviruses are the best sources of these peptides reaching more than 80% of CPP sequence coverage per protein. Selected sequences were tested experimentally and validated the results. Overall, this study reveals that viruses form a natural multivalent biotechnological platform still underexplored in drug discovery and the heterogeneous abundance of CPP/AMP sequences among viral families opens new avenues in viral biology research.
Autores principais:Freire, João Miguel
Outros Autores:Dias, Susana Almeida; Flores, Luís; Veiga, Ana Salomé; Castanho, Miguel A. R. B.
Ano:2015
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
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author Freire, João Miguel
author2 Dias, Susana Almeida
Flores, Luís
Veiga, Ana Salomé
Castanho, Miguel A. R. B.
author2_role author
author
author
author
author_facet Freire, João Miguel
Dias, Susana Almeida
Flores, Luís
Veiga, Ana Salomé
Castanho, Miguel A. R. B.
author_role author
contributor_name_str_mv Repositório Científico de Acesso Aberto da ULisboa
country_str PT
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datacite.contributors.contributor.contributorName.fl_str_mv Repositório Científico de Acesso Aberto da ULisboa
datacite.creators.creator.creatorName.fl_str_mv Freire, João Miguel
Dias, Susana Almeida
Flores, Luís
Veiga, Ana Salomé
Castanho, Miguel A. R. B.
datacite.date.Accepted.fl_str_mv 2015-01-01T00:00:00Z
datacite.date.available.fl_str_mv 2016-03-18T15:01:49Z
datacite.date.embargoed.fl_str_mv 2016-03-18T15:01:49Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_16ec
datacite.titles.title.fl_str_mv Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
dc.contributor.none.fl_str_mv Repositório Científico de Acesso Aberto da ULisboa
dc.creator.none.fl_str_mv Freire, João Miguel
Dias, Susana Almeida
Flores, Luís
Veiga, Ana Salomé
Castanho, Miguel A. R. B.
dc.date.Accepted.fl_str_mv 2015-01-01T00:00:00Z
dc.date.available.fl_str_mv 2016-03-18T15:01:49Z
dc.date.embargoed.fl_str_mv 2016-03-18T15:01:49Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10451/23081
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Oxford University Press
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_16ec
dc.title.fl_str_mv Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description Motivation: The need for more effective and safer pharmaceuticals is a persistent quest. Microbial adaptations create the need to permanently develop new antimicrobials, for instance. Similarly, intracellular delivery of drugs is still a challenge and translocation of membranes for drug delivery is an area of intense research. Peptides can be used both as antimicrobial drug leads and drug carrier systems for intracellular delivery. Multifunctional proteins are abundant in viruses but, surprisingly, have never been thoroughly screened for bioactive peptide sequences. Results: Using the AMPA and CellPPD online tools we have evaluated the propensity of viral proteins to comprise antimicrobial (AMP) or cell-penetrating peptides (CPP). Capsid proteins from both enveloped and non-enveloped viruses, and membrane and envelope proteins from enveloped viruses, in a total of 272 proteins from 133 viruses, were screened to detect the presence of potential AMP and CPP sequences. A pool of 2444 and 426 CPP and AMP sequences, respectively, were discovered. The capsids of flaviviruses are the best sources of these peptides reaching more than 80% of CPP sequence coverage per protein. Selected sequences were tested experimentally and validated the results. Overall, this study reveals that viruses form a natural multivalent biotechnological platform still underexplored in drug discovery and the heterogeneous abundance of CPP/AMP sequences among viral families opens new avenues in viral biology research.
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person_str_mv Freire, João Miguel
Dias, Susana Almeida
Flores, Luís
Veiga, Ana Salomé
Castanho, Miguel A. R. B.
publishDate 2015
publisher.none.fl_str_mv Oxford University Press
reponame_str Repositório da Universidade de Lisboa
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spelling engOxford University Presspt_PTMotivation: The need for more effective and safer pharmaceuticals is a persistent quest. Microbial adaptations create the need to permanently develop new antimicrobials, for instance. Similarly, intracellular delivery of drugs is still a challenge and translocation of membranes for drug delivery is an area of intense research. Peptides can be used both as antimicrobial drug leads and drug carrier systems for intracellular delivery. Multifunctional proteins are abundant in viruses but, surprisingly, have never been thoroughly screened for bioactive peptide sequences. Results: Using the AMPA and CellPPD online tools we have evaluated the propensity of viral proteins to comprise antimicrobial (AMP) or cell-penetrating peptides (CPP). Capsid proteins from both enveloped and non-enveloped viruses, and membrane and envelope proteins from enveloped viruses, in a total of 272 proteins from 133 viruses, were screened to detect the presence of potential AMP and CPP sequences. A pool of 2444 and 426 CPP and AMP sequences, respectively, were discovered. The capsids of flaviviruses are the best sources of these peptides reaching more than 80% of CPP sequence coverage per protein. Selected sequences were tested experimentally and validated the results. Overall, this study reveals that viruses form a natural multivalent biotechnological platform still underexplored in drug discovery and the heterogeneous abundance of CPP/AMP sequences among viral families opens new avenues in viral biology research.application/pdfpt_PTMining viral proteins for antimicrobial and cell-penetrating drug delivery peptidesFreire, João MiguelDias, Susana AlmeidaFlores, LuísVeiga, Ana SaloméCastanho, Miguel A. R. B.HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptISSNIsPartOf1367-4803DOIIsPartOf10.1093/bioinformatics/btv1312016-03-18T15:01:49Z20152015-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/23081http://purl.org/coar/access_right/c_16ecrestricted access196746 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/b14cba1a-6af9-4ffe-85cd-c74bc78ef930/downloadBioinformatics
spellingShingle Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
Freire, João Miguel
status SINGLETON
title Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
title_full Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
title_fullStr Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
title_full_unstemmed Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
title_short Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
title_sort Mining viral proteins for antimicrobial and cell-penetrating drug delivery peptides
url http://hdl.handle.net/10451/23081
visible 1