Inhibitors for Bacterial Cell-Wall Recycling

Autores
Yamaguchi, Takao; Blázquez, Blas; Hesek, Dusan; Lee, Mijoon; Llarrull, Leticia Irene; Boggess, Bill; Oliver, Allen G.; Fisher, Jed F.; Mobashery, Shahriar
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Gram-negative bacteria have evolved an elaborate process for the recycling of their cell wall, which is initiated in the periplasmic space by the action of lytic transglycosylases. The product of this reaction, beta-D-N-acetylglucosamine-(1→4)-1,6-anhydro-beta-D-Nacetylmuramyl-L-Ala-gama-D-Glu-meso-DAP-D-Ala-D-Ala (compound 1), is internalized to begin the recycling events within the cytoplasm. The first step in the cytoplasmic recycling is catalyzed by the NagZ glycosylase, which cleaves in a hydrolytic reaction the N-acetylglucosamine glycosidic bond of metabolite 1. The reactions catalyzed by both the lytic glycosylases and NagZ are believed to involve oxocarbenium transition species. We describe herein the synthesis and evaluation of four iminosaccharides as possible mimetics of the oxocarbenium species, and we disclose one as a potent (compound 3, Ki = 300 ± 15 nM) competitive inhibitor of NagZ.
Fil: Yamaguchi, Takao. University of Notre Dame-Indiana; Estados Unidos
Fil: Blázquez, Blas. University of Notre Dame-Indiana; Estados Unidos
Fil: Hesek, Dusan. University of Notre Dame-Indiana; Estados Unidos
Fil: Lee, Mijoon. University of Notre Dame-Indiana; Estados Unidos
Fil: Llarrull, Leticia Irene. University of Notre Dame-Indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Boggess, Bill. University of Notre Dame-Indiana; Estados Unidos
Fil: Oliver, Allen G.. University of Notre Dame-Indiana; Estados Unidos
Fil: Fisher, Jed F.. University of Notre Dame-Indiana; Estados Unidos
Fil: Mobashery, Shahriar. University of Notre Dame-Indiana; Estados Unidos
Materia
Iminosaccharide
NagZ
MltB
peptidoglycan
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:11336/268636
Acceder
id CONICETDig_6b1520266ba0a69c7bbf062d34310d81
oai_identifier_str oai:ri.conicet.gov.ar:11336/268636
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibitors for Bacterial Cell-Wall RecyclingYamaguchi, TakaoBlázquez, BlasHesek, DusanLee, MijoonLlarrull, Leticia IreneBoggess, BillOliver, Allen G.Fisher, Jed F.Mobashery, ShahriarIminosaccharideNagZMltBpeptidoglycanhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Gram-negative bacteria have evolved an elaborate process for the recycling of their cell wall, which is initiated in the periplasmic space by the action of lytic transglycosylases. The product of this reaction, beta-D-N-acetylglucosamine-(1→4)-1,6-anhydro-beta-D-Nacetylmuramyl-L-Ala-gama-D-Glu-meso-DAP-D-Ala-D-Ala (compound 1), is internalized to begin the recycling events within the cytoplasm. The first step in the cytoplasmic recycling is catalyzed by the NagZ glycosylase, which cleaves in a hydrolytic reaction the N-acetylglucosamine glycosidic bond of metabolite 1. The reactions catalyzed by both the lytic glycosylases and NagZ are believed to involve oxocarbenium transition species. We describe herein the synthesis and evaluation of four iminosaccharides as possible mimetics of the oxocarbenium species, and we disclose one as a potent (compound 3, Ki = 300 ± 15 nM) competitive inhibitor of NagZ.Fil: Yamaguchi, Takao. University of Notre Dame-Indiana; Estados UnidosFil: Blázquez, Blas. University of Notre Dame-Indiana; Estados UnidosFil: Hesek, Dusan. University of Notre Dame-Indiana; Estados UnidosFil: Lee, Mijoon. University of Notre Dame-Indiana; Estados UnidosFil: Llarrull, Leticia Irene. University of Notre Dame-Indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Boggess, Bill. University of Notre Dame-Indiana; Estados UnidosFil: Oliver, Allen G.. University of Notre Dame-Indiana; Estados UnidosFil: Fisher, Jed F.. University of Notre Dame-Indiana; Estados UnidosFil: Mobashery, Shahriar. University of Notre Dame-Indiana; Estados UnidosAmerican Chemical Society2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/268636Yamaguchi, Takao; Blázquez, Blas; Hesek, Dusan; Lee, Mijoon; Llarrull, Leticia Irene; et al.; Inhibitors for Bacterial Cell-Wall Recycling; American Chemical Society; ACS Medicinal Chemistry Letters; 3; 3; 1-2012; 238-2421948-5875CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/ml2002746info:eu-repo/semantics/altIdentifier/doi/10.1021/ml2002746info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:46:41Zoai:ri.conicet.gov.ar:11336/268636instacron: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:34982025-10-15 15:46:41.364CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibitors for Bacterial Cell-Wall Recycling
title Inhibitors for Bacterial Cell-Wall Recycling
spellingShingle Inhibitors for Bacterial Cell-Wall Recycling
Yamaguchi, Takao
Iminosaccharide
NagZ
MltB
peptidoglycan
title_short Inhibitors for Bacterial Cell-Wall Recycling
title_full Inhibitors for Bacterial Cell-Wall Recycling
title_fullStr Inhibitors for Bacterial Cell-Wall Recycling
title_full_unstemmed Inhibitors for Bacterial Cell-Wall Recycling
title_sort Inhibitors for Bacterial Cell-Wall Recycling
dc.creator.none.fl_str_mv Yamaguchi, Takao
Blázquez, Blas
Hesek, Dusan
Lee, Mijoon
Llarrull, Leticia Irene
Boggess, Bill
Oliver, Allen G.
Fisher, Jed F.
Mobashery, Shahriar
author Yamaguchi, Takao
author_facet Yamaguchi, Takao
Blázquez, Blas
Hesek, Dusan
Lee, Mijoon
Llarrull, Leticia Irene
Boggess, Bill
Oliver, Allen G.
Fisher, Jed F.
Mobashery, Shahriar
author_role author
author2 Blázquez, Blas
Hesek, Dusan
Lee, Mijoon
Llarrull, Leticia Irene
Boggess, Bill
Oliver, Allen G.
Fisher, Jed F.
Mobashery, Shahriar
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Iminosaccharide
NagZ
MltB
peptidoglycan
topic Iminosaccharide
NagZ
MltB
peptidoglycan
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Gram-negative bacteria have evolved an elaborate process for the recycling of their cell wall, which is initiated in the periplasmic space by the action of lytic transglycosylases. The product of this reaction, beta-D-N-acetylglucosamine-(1→4)-1,6-anhydro-beta-D-Nacetylmuramyl-L-Ala-gama-D-Glu-meso-DAP-D-Ala-D-Ala (compound 1), is internalized to begin the recycling events within the cytoplasm. The first step in the cytoplasmic recycling is catalyzed by the NagZ glycosylase, which cleaves in a hydrolytic reaction the N-acetylglucosamine glycosidic bond of metabolite 1. The reactions catalyzed by both the lytic glycosylases and NagZ are believed to involve oxocarbenium transition species. We describe herein the synthesis and evaluation of four iminosaccharides as possible mimetics of the oxocarbenium species, and we disclose one as a potent (compound 3, Ki = 300 ± 15 nM) competitive inhibitor of NagZ.
Fil: Yamaguchi, Takao. University of Notre Dame-Indiana; Estados Unidos
Fil: Blázquez, Blas. University of Notre Dame-Indiana; Estados Unidos
Fil: Hesek, Dusan. University of Notre Dame-Indiana; Estados Unidos
Fil: Lee, Mijoon. University of Notre Dame-Indiana; Estados Unidos
Fil: Llarrull, Leticia Irene. University of Notre Dame-Indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Boggess, Bill. University of Notre Dame-Indiana; Estados Unidos
Fil: Oliver, Allen G.. University of Notre Dame-Indiana; Estados Unidos
Fil: Fisher, Jed F.. University of Notre Dame-Indiana; Estados Unidos
Fil: Mobashery, Shahriar. University of Notre Dame-Indiana; Estados Unidos
description Gram-negative bacteria have evolved an elaborate process for the recycling of their cell wall, which is initiated in the periplasmic space by the action of lytic transglycosylases. The product of this reaction, beta-D-N-acetylglucosamine-(1→4)-1,6-anhydro-beta-D-Nacetylmuramyl-L-Ala-gama-D-Glu-meso-DAP-D-Ala-D-Ala (compound 1), is internalized to begin the recycling events within the cytoplasm. The first step in the cytoplasmic recycling is catalyzed by the NagZ glycosylase, which cleaves in a hydrolytic reaction the N-acetylglucosamine glycosidic bond of metabolite 1. The reactions catalyzed by both the lytic glycosylases and NagZ are believed to involve oxocarbenium transition species. We describe herein the synthesis and evaluation of four iminosaccharides as possible mimetics of the oxocarbenium species, and we disclose one as a potent (compound 3, Ki = 300 ± 15 nM) competitive inhibitor of NagZ.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/268636
Yamaguchi, Takao; Blázquez, Blas; Hesek, Dusan; Lee, Mijoon; Llarrull, Leticia Irene; et al.; Inhibitors for Bacterial Cell-Wall Recycling; American Chemical Society; ACS Medicinal Chemistry Letters; 3; 3; 1-2012; 238-242
1948-5875
CONICET Digital
CONICET
url http://hdl.handle.net/11336/268636
identifier_str_mv Yamaguchi, Takao; Blázquez, Blas; Hesek, Dusan; Lee, Mijoon; Llarrull, Leticia Irene; et al.; Inhibitors for Bacterial Cell-Wall Recycling; American Chemical Society; ACS Medicinal Chemistry Letters; 3; 3; 1-2012; 238-242
1948-5875
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://pubs.acs.org/doi/10.1021/ml2002746
info:eu-repo/semantics/altIdentifier/doi/10.1021/ml2002746
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 American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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_ 1846083563365072896
score 13.22299

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