Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs

Livestock diseases caused by Trypanosoma congolense , T . vivax and T . brucei , collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under...

Full description

Saved in:
Bibliographic Details
Published inPLoS pathogens Vol. 16; no. 11; p. e1008932
Main Authors Giordani, Federica, Paape, Daniel, Vincent, Isabel M., Pountain, Andrew W., Fernández-Cortés, Fernando, Rico, Eva, Zhang, Ning, Morrison, Liam J., Freund, Yvonne, Witty, Michael J., Peter, Rosemary, Edwards, Darren Y., Wilkes, Jonathan M., van der Hooft, Justin J. J., Regnault, Clément, Read, Kevin D., Horn, David, Field, Mark C., Barrett, Michael P.
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 03.11.2020
Public Library of Science (PLoS)
Subjects
Aldehyde dehydrogenase
Aldehydes
Analysis
Animals
Biology and Life Sciences
Boron Compounds - metabolism
Carboxylic Acids - metabolism
Carboxypeptidase
Carboxypeptidases - metabolism
Chemical compounds
Chemical properties
Chromosome 10
Chromosomes
Cloning
Dosage and administration
Drug dosages
Drug Resistance
Drug therapy
Drugs
Enzyme activation
Female
Forecasts and trends
Gene sequencing
Genes
Genomes
Identification and classification
Infectious diseases
Influence
Livestock
Metabolism
Metabolomics
Methionine
Methylation
Mice
Nucleotide sequence
Parasitemia - veterinary
Parasites
Peptidase
Peptidases
Peptides
Physical Sciences
Prodrugs
Prodrugs - metabolism
Proteases
Protozoan Proteins - metabolism
Research and Analysis Methods
RNA processing
Serine
Serine carboxypeptidase
Splicing
Synteny
Trypanocidal Agents - metabolism
Trypanosoma
Trypanosoma brucei brucei - drug effects
Trypanosoma brucei brucei - enzymology
Trypanosoma congolense - drug effects
Trypanosoma congolense - enzymology
Trypanosoma vivax - drug effects
Trypanosoma vivax - enzymology
Trypanosomiasis, African - drug therapy
Trypanosomiasis, African - parasitology
Trypanosomiasis, African - veterinary
Valine - analogs & derivatives
Valine - metabolism
Veterinary research
Whole genome sequencing
United Kingdom
Online AccessGet full text
ISSN1553-7374
1553-7366
1553-7374
DOI10.1371/journal.ppat.1008932

Cover

Abstract Livestock diseases caused by Trypanosoma congolense , T . vivax and T . brucei , collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T . brucei , due to partial deletion within the locus containing three tandem copies of the CBP genes. T . congolense parasites, which possess a larger array of related CBPs , also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T . brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T . brucei or T . congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.
AbstractList In Trypanosoma brucei treated with acoziborole, metabolomics experiments revealed a profound change in methionine metabolism [22], that may relate to RNA processing defects, given multi-methylation of the spliced leader sequence used for trans-splicing by trypanosomatids [23]. A trypanocidal benzoxaborole, of the amino-methyl subclass, was shown to be subject to two-step metabolic processing, involving a primary conversion by an amine oxidase in host serum to an aldehyde, that is further metabolised to a carboxylate via T. brucei aldehyde dehydrogenase [24]. Resistant trypanosomes share genetic changes in a tandem array of serine carboxypeptidase (CBP) genes Genome sequencing of the two T. brucei resistant clones TbOXR_A and TbOXR_C revealed a notable reduction of read depth in a region on chromosome 10 where a tandem repeat of the three serine peptidases TbCBP1A, TbCBP1B and TbCBP1C (Tb927.10.1030–1050 respectively) is present (Fig 2A). (B) Coverage plot as in (A) but with T. congolense wild type (both parent, TcoWT, and high passage, TcoWT_HP) and AN11736-resistant lines (TcoOXR_A, TcoOXR_B). https://doi.org/10.1371/journal.ppat.1008932.g002 Genome sequencing of the T. congolense resistant clones TcoOXR_B and TcoOXR_C and the parent lines (TcoWT, cultured for a limited number of passages, and TcoWT_HP, high passage, maintained in culture for the same time required for drug resistance selection), revealed reduced read coverage across the syntenic region of chromosome 10.
In Trypanosoma brucei treated with acoziborole, metabolomics experiments revealed a profound change in methionine metabolism [22], that may relate to RNA processing defects, given multi-methylation of the spliced leader sequence used for trans-splicing by trypanosomatids [23]. A trypanocidal benzoxaborole, of the amino-methyl subclass, was shown to be subject to two-step metabolic processing, involving a primary conversion by an amine oxidase in host serum to an aldehyde, that is further metabolised to a carboxylate via T. brucei aldehyde dehydrogenase [24]. Resistant trypanosomes share genetic changes in a tandem array of serine carboxypeptidase (CBP) genes Genome sequencing of the two T. brucei resistant clones TbOXR_A and TbOXR_C revealed a notable reduction of read depth in a region on chromosome 10 where a tandem repeat of the three serine peptidases TbCBP1A, TbCBP1B and TbCBP1C (Tb927.10.1030–1050 respectively) is present (Fig 2A). (B) Coverage plot as in (A) but with T. congolense wild type (both parent, TcoWT, and high passage, TcoWT_HP) and AN11736-resistant lines (TcoOXR_A, TcoOXR_B). https://doi.org/10.1371/journal.ppat.1008932.g002 Genome sequencing of the T. congolense resistant clones TcoOXR_B and TcoOXR_C and the parent lines (TcoWT, cultured for a limited number of passages, and TcoWT_HP, high passage, maintained in culture for the same time required for drug resistance selection), revealed reduced read coverage across the syntenic region of chromosome 10.
Livestock diseases caused by Trypanosoma congolense , T . vivax and T . brucei , collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T . brucei , due to partial deletion within the locus containing three tandem copies of the CBP genes. T . congolense parasites, which possess a larger array of related CBPs , also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T . brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T . brucei or T . congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.
Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.
Livestock diseases caused by Trypanosoma congolense , T . vivax and T . brucei , collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T . brucei , due to partial deletion within the locus containing three tandem copies of the CBP genes. T . congolense parasites, which possess a larger array of related CBPs , also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T . brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T . brucei or T . congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism. AN11736 is a member of the benzoxaborole class identified as a development candidate for animal African trypanosomiasis, a deadly livestock disease with huge economic impact. As part of its early evaluation phase, we set to unravel the risk and mode of resistance to this new trypanocide. We discovered that AN11736 behaves as a prodrug that, once inside trypanosomes, is cleaved by the activity of specific serine carboxypeptidases. AN11736-resistant Trypanosoma brucei and T . congolense had deletions within the serine carboxypeptidase gene array, resulting in their being unable to efficiently process the parent drug. Other benzoxaboroles with a similar sub-structure are also substrates for the serine carboxypeptidases, hence our findings assume great importance in considering the future development and deployment of this class of compounds.
Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.
Audience Academic
Author Paape, Daniel
Read, Kevin D.
van der Hooft, Justin J. J.
Horn, David
Freund, Yvonne
Edwards, Darren Y.
Witty, Michael J.
Regnault, Clément
Rico, Eva
Fernández-Cortés, Fernando
Peter, Rosemary
Barrett, Michael P.
Morrison, Liam J.
Giordani, Federica
Vincent, Isabel M.
Wilkes, Jonathan M.
Field, Mark C.
Pountain, Andrew W.
Zhang, Ning
AuthorAffiliation University of Geneva, SWITZERLAND
8 Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, České Budějovice, Czech Republic
7 Current address: Bioinformatics Group, Wageningen University, Wageningen, the Netherlands
6 Glasgow Polyomics, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
1 Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
4 Anacor Pharmaceuticals, Inc., Palo Alto, California, United States of America
2 Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, United Kingdom
3 Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom
5 Global Alliance for Livestock and Veterinary Medicine, Pentlands Science Park, Penicuik, Edinburgh, United Kingdom
AuthorAffiliation_xml – name: 3 Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom
– name: 1 Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
– name: 6 Glasgow Polyomics, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
– name: 4 Anacor Pharmaceuticals, Inc., Palo Alto, California, United States of America
– name: University of Geneva, SWITZERLAND
– name: 5 Global Alliance for Livestock and Veterinary Medicine, Pentlands Science Park, Penicuik, Edinburgh, United Kingdom
– name: 7 Current address: Bioinformatics Group, Wageningen University, Wageningen, the Netherlands
– name: 8 Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, České Budějovice, Czech Republic
– name: 2 Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, United Kingdom
Author_xml – sequence: 1
  givenname: Federica
  orcidid: 0000-0001-9964-281X
  surname: Giordani
  fullname: Giordani, Federica
– sequence: 2
  givenname: Daniel
  orcidid: 0000-0003-4355-8058
  surname: Paape
  fullname: Paape, Daniel
– sequence: 3
  givenname: Isabel M.
  orcidid: 0000-0003-2663-4389
  surname: Vincent
  fullname: Vincent, Isabel M.
– sequence: 4
  givenname: Andrew W.
  orcidid: 0000-0001-9651-5145
  surname: Pountain
  fullname: Pountain, Andrew W.
– sequence: 5
  givenname: Fernando
  orcidid: 0000-0001-9362-2164
  surname: Fernández-Cortés
  fullname: Fernández-Cortés, Fernando
– sequence: 6
  givenname: Eva
  surname: Rico
  fullname: Rico, Eva
– sequence: 7
  givenname: Ning
  surname: Zhang
  fullname: Zhang, Ning
– sequence: 8
  givenname: Liam J.
  orcidid: 0000-0002-8304-9066
  surname: Morrison
  fullname: Morrison, Liam J.
– sequence: 9
  givenname: Yvonne
  surname: Freund
  fullname: Freund, Yvonne
– sequence: 10
  givenname: Michael J.
  orcidid: 0000-0003-4094-7154
  surname: Witty
  fullname: Witty, Michael J.
– sequence: 11
  givenname: Rosemary
  surname: Peter
  fullname: Peter, Rosemary
– sequence: 12
  givenname: Darren Y.
  orcidid: 0000-0001-8245-8928
  surname: Edwards
  fullname: Edwards, Darren Y.
– sequence: 13
  givenname: Jonathan M.
  surname: Wilkes
  fullname: Wilkes, Jonathan M.
– sequence: 14
  givenname: Justin J. J.
  orcidid: 0000-0002-9340-5511
  surname: van der Hooft
  fullname: van der Hooft, Justin J. J.
– sequence: 15
  givenname: Clément
  surname: Regnault
  fullname: Regnault, Clément
– sequence: 16
  givenname: Kevin D.
  orcidid: 0000-0002-8536-0130
  surname: Read
  fullname: Read, Kevin D.
– sequence: 17
  givenname: David
  orcidid: 0000-0001-5173-9284
  surname: Horn
  fullname: Horn, David
– sequence: 18
  givenname: Mark C.
  orcidid: 0000-0002-4866-2885
  surname: Field
  fullname: Field, Mark C.
– sequence: 19
  givenname: Michael P.
  orcidid: 0000-0001-9447-3519
  surname: Barrett
  fullname: Barrett, Michael P.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33141865$$D View this record in MEDLINE/PubMed
BookMark eNqVkk9v1DAQxS1URNuFb4BgJS5w2MWOnTjhgFRVUFaqQOLf1Zo448WrbJzaTtXy6XHYtOpWFRLKwZH9m-eZ53dMDjrXISHPGV0yLtnbjRt8B-2y7yEuGaVlxbNH5IjlOV9ILsXBnf9DchzChlLBOCuekEPOmWBlkR-Rs58Y0dsO_PU8-useOqdtA-28xu63u4LaeddimIPHeY99TGcBF6CjvYSIzbz3rvHDOjwljw20AZ9N64z8-Pjh--mnxfmXs9XpyflCFwWLC9OYuqoyJk2NuUGGYLSpG1pTNCVvkDHIaQkaDK8lCEM1FBIzrKDOmKgyPiMvd7p964KaPAgqE7ISRZVnI7HaEY2Djeq93abZlAOr_m44v1bgo9UtKsgbBqAFUNMIWWdVISsEIYvUEctTQzPyfrptqLfYaOyih3ZPdP-ks7_U2l0qKRlllCeB15OAdxcDhqi2NmhsW-jQDWPfuSzSxCVN6Kt76MPTTdQa0gC2My7dq0dRdVIIzpNFpUzU8gEqfQ1urU45Mjbt7xW82StITMSruIYhBLX69vU_2M_77Iu7Bt46dxPABIgdoL0LwaO5RRhVY85vXFBjztWU81T27l6ZthGideMz2PbfxX8APA0G0w
CitedBy_id crossref_primary_10_1186_s12864_024_10862_6
crossref_primary_10_1186_s13104_022_06258_y
crossref_primary_10_1016_j_pt_2024_06_013
crossref_primary_10_1016_j_pt_2021_09_002
crossref_primary_10_3389_fvets_2022_868912
crossref_primary_10_1371_journal_pntd_0012541
crossref_primary_10_1016_j_jmgm_2021_108104
crossref_primary_10_1016_j_ijpddr_2024_100533
crossref_primary_10_1016_j_pt_2021_04_007
crossref_primary_10_1021_acsmedchemlett_4c00111
crossref_primary_10_1016_j_ijpddr_2023_10_003
crossref_primary_10_1038_s41564_022_01211_y
crossref_primary_10_1371_journal_pntd_0009939
crossref_primary_10_1038_s41579_022_00777_y
crossref_primary_10_1016_j_ejmech_2023_115761
crossref_primary_10_1016_j_pt_2024_07_003
crossref_primary_10_3390_ijms23052844
crossref_primary_10_1042_BST20220618
crossref_primary_10_3390_microorganisms9071408
crossref_primary_10_3390_ph16071046
Cites_doi 10.1007/BF02907561
10.1371/journal.pntd.0000618
10.1038/s41598-018-26303-w
10.1093/nar/gki996
10.1016/S0140-6736(17)31510-6
10.1016/j.bbapap.2011.05.011
10.2217/fmb.11.20
10.1093/bioinformatics/btx499
10.1017/S0031182016001268
10.1093/nar/gkr987
10.1021/ml100013s
10.1016/j.molbiopara.2010.09.002
10.1093/bioinformatics/bts069
10.1371/journal.ppat.1003886
10.1016/j.bmc.2014.04.065
10.1093/bioinformatics/btr703
10.1093/genetics/142.3.693
10.1128/AAC.02058-12
10.1128/AAC.00044-13
10.1371/journal.pntd.0006925
10.1371/journal.pntd.0006450
10.1016/j.ijpddr.2019.02.002
10.1371/journal.pntd.0001151
10.1016/S0166-6851(03)00175-0
10.1038/nprot.2015.005
10.1371/journal.ppat.1007315
10.1016/j.bmcl.2017.11.028
10.1073/pnas.1807915115
10.1038/ncomms14574
10.1080/13543776.2018.1473379
10.1126/science.1142189
10.1093/bioinformatics/btt656
10.1371/journal.pntd.0004299
10.1016/j.bmcl.2011.02.024
10.1371/journal.ppat.1006850
10.1021/bi00203a007
10.4155/fmc.11.80
10.1093/bioinformatics/btp352
10.1371/journal.ppat.1005971
10.1016/0076-6879(94)44020-4
10.1038/nmeth.1923
10.1093/oxfordjournals.jbchem.a022133
10.15252/emmm.201607370
10.1038/nature10771
ContentType Journal Article
Copyright COPYRIGHT 2020 Public Library of Science
2020 Giordani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2020 Giordani et al 2020 Giordani et al
Copyright_xml – notice: COPYRIGHT 2020 Public Library of Science
– notice: 2020 Giordani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2020 Giordani et al 2020 Giordani et al
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
ISN
ISR
3V.
7QL
7U9
7X7
7XB
88E
8FE
8FH
8FI
8FJ
8FK
ABUWG
AEUYN
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
C1K
CCPQU
DWQXO
FYUFA
GHDGH
GNUQQ
H94
HCIFZ
K9.
LK8
M0S
M1P
M7P
PHGZM
PHGZT
PIMPY
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
7X8
5PM
DOA
DOI 10.1371/journal.ppat.1008932
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Gale In Context: Canada
Gale In Context: Science
ProQuest Central (Corporate)
Bacteriology Abstracts (Microbiology B)
Virology and AIDS Abstracts
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
ProQuest SciTech Collection
ProQuest Natural Science Collection
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest One Sustainability
ProQuest Central UK/Ireland
ProQuest Central Essentials - QC
Biological Science Collection
ProQuest Central
Natural Science Collection
Environmental Sciences and Pollution Management
ProQuest One Community College
ProQuest Central Korea
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
AIDS and Cancer Research Abstracts
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
Biological Sciences
Health & Medical Collection (Alumni)
Medical Database
Biological Science Database
ProQuest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Publicly Available Content Database
ProQuest Central Student
ProQuest One Academic Middle East (New)
ProQuest Central Essentials
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Natural Science Collection
ProQuest Central China
Environmental Sciences and Pollution Management
ProQuest Central
ProQuest One Applied & Life Sciences
ProQuest One Sustainability
ProQuest Health & Medical Research Collection
Health Research Premium Collection
Health and Medicine Complete (Alumni Edition)
Natural Science Collection
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Health & Medical Research Collection
Biological Science Collection
AIDS and Cancer Research Abstracts
ProQuest Central (New)
ProQuest Medical Library (Alumni)
Virology and AIDS Abstracts
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Biological Science Database
ProQuest SciTech Collection
ProQuest Hospital Collection (Alumni)
ProQuest Health & Medical Complete
ProQuest Medical Library
ProQuest One Academic UKI Edition
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList Publicly Available Content Database

CrossRef


MEDLINE
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 4
  dbid: BENPR
  name: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
DocumentTitleAlternate Peptidase-activated trypanocidal benzoxaboroles
EISSN 1553-7374
ExternalDocumentID 2479469522
oai_doaj_org_article_a5d1aac4a0fd47b29679ea476bd015f8
PMC7710103
A643392387
33141865
10_1371_journal_ppat_1008932
Genre Research Support, Non-U.S. Gov't
Journal Article
GeographicLocations United Kingdom
GeographicLocations_xml – name: United Kingdom
GrantInformation_xml – fundername: Wellcome Trust
  grantid: 104111/Z/14/ Z
– fundername: Biotechnology and Biological Sciences Research Council
  grantid: BB/S001034/1
– fundername: Wellcome Trust
  grantid: 203134/Z/ 16/Z
– fundername: Medical Research Council
  grantid: MR/L018853/1
– fundername: Wellcome Trust
  grantid: 203134/Z/16/Z
– fundername: Medical Research Council
  grantid: MR/S019650/1
– fundername: Wellcome Trust
  grantid: 100320/Z/ 12/Z
– fundername: ;
  grantid: 203134/Z/16/Z
– fundername: ;
  grantid: BB/S001034/1
– fundername: ;
  grantid: 100320/Z/12/Z
– fundername: ;
  grantid: BB/S001034/1)
– fundername: ;
  grantid: 104111/Z/14/Z
GroupedDBID ---
123
29O
2WC
53G
5VS
7X7
88E
8FE
8FH
8FI
8FJ
AAFWJ
AAUCC
AAWOE
AAYXX
ABDBF
ABUWG
ACGFO
ACIHN
ACPRK
ACUHS
ADBBV
AEAQA
AENEX
AEUYN
AFKRA
AFPKN
AFRAH
AHMBA
ALMA_UNASSIGNED_HOLDINGS
AOIJS
B0M
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
BWKFM
CCPQU
CITATION
CS3
DIK
DU5
E3Z
EAP
EAS
EBD
EMK
EMOBN
ESX
F5P
FPL
FYUFA
GROUPED_DOAJ
GX1
HCIFZ
HMCUK
HYE
IAO
IHR
INH
INR
ISN
ISR
ITC
KQ8
LK8
M1P
M48
M7P
MM.
O5R
O5S
OK1
OVT
P2P
PGMZT
PHGZM
PHGZT
PIMPY
PQQKQ
PROAC
PSQYO
PV9
QF4
QN7
RNS
RPM
RZL
SV3
TR2
TUS
UKHRP
WOW
~8M
ADRAZ
CGR
CUY
CVF
ECM
EIF
H13
IPNFZ
NPM
PJZUB
PPXIY
PQGLB
RIG
WOQ
PUEGO
PMFND
3V.
7QL
7U9
7XB
8FK
AZQEC
C1K
DWQXO
GNUQQ
H94
K9.
PKEHL
PQEST
PQUKI
PRINS
7X8
5PM
-
AAPBV
ABPTK
ADACO
BBAFP
M~E
ID FETCH-LOGICAL-c661t-fdfb99217fbe5fe1eafcfbd0b0ef83de11a508acaf3b7a4f0ca67e2e9ab214923
IEDL.DBID M48
ISSN 1553-7374
1553-7366
IngestDate Sun Apr 03 16:01:45 EDT 2022
Wed Aug 27 00:44:18 EDT 2025
Thu Aug 21 13:25:13 EDT 2025
Thu Sep 04 23:48:55 EDT 2025
Fri Jul 25 09:13:23 EDT 2025
Tue Jun 17 21:28:45 EDT 2025
Tue Jun 10 20:30:19 EDT 2025
Fri Jun 27 04:06:17 EDT 2025
Sat Sep 06 07:19:17 EDT 2025
Mon Jul 21 06:05:00 EDT 2025
Tue Jul 01 04:24:24 EDT 2025
Thu Apr 24 22:57:15 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 11
Language English
License This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creative Commons Attribution License
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c661t-fdfb99217fbe5fe1eafcfbd0b0ef83de11a508acaf3b7a4f0ca67e2e9ab214923
Notes new_version
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
The authors have declared that no competing interests exist.
ORCID 0000-0001-9964-281X
0000-0002-9340-5511
0000-0001-9651-5145
0000-0001-5173-9284
0000-0002-4866-2885
0000-0003-2663-4389
0000-0001-8245-8928
0000-0003-4094-7154
0000-0003-4355-8058
0000-0002-8304-9066
0000-0001-9362-2164
0000-0002-8536-0130
0000-0001-9447-3519
OpenAccessLink http://journals.scholarsportal.info/openUrl.xqy?doi=10.1371/journal.ppat.1008932
PMID 33141865
PQID 2479469522
PQPubID 1436335
ParticipantIDs plos_journals_2479469522
doaj_primary_oai_doaj_org_article_a5d1aac4a0fd47b29679ea476bd015f8
pubmedcentral_primary_oai_pubmedcentral_nih_gov_7710103
proquest_miscellaneous_2457650880
proquest_journals_2479469522
gale_infotracmisc_A643392387
gale_infotracacademiconefile_A643392387
gale_incontextgauss_ISR_A643392387
gale_incontextgauss_ISN_A643392387
pubmed_primary_33141865
crossref_primary_10_1371_journal_ppat_1008932
crossref_citationtrail_10_1371_journal_ppat_1008932
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2020-11-03
PublicationDateYYYYMMDD 2020-11-03
PublicationDate_xml – month: 11
  year: 2020
  text: 2020-11-03
  day: 03
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: San Francisco
– name: San Francisco, CA USA
PublicationTitle PLoS pathogens
PublicationTitleAlternate PLoS Pathog
PublicationYear 2020
Publisher Public Library of Science
Public Library of Science (PLoS)
Publisher_xml – name: Public Library of Science
– name: Public Library of Science (PLoS)
References PC Steketee (ppat.1008932.ref022) 2018; 12
DJ Creek (ppat.1008932.ref036) 2013; 57
T Carver (ppat.1008932.ref044) 2012; 28
JQ Del Rosso (ppat.1008932.ref008) 2014; 7
RT Jacobs (ppat.1008932.ref010) 2011; 3
S Alsford (ppat.1008932.ref026) 2012; 482
VE Alvarez (ppat.1008932.ref034) 2012; 1824
F Giordani (ppat.1008932.ref003) 2016; 143
Y Gloaguen (ppat.1008932.ref047) 2017; 33
A Nocentini (ppat.1008932.ref005) 2018; 28
ND Rawlings (ppat.1008932.ref042) 2012; 40
V Hernandez (ppat.1008932.ref020) 2013; 57
K. Breddam (ppat.1008932.ref032) 1986; 51
N Zhang (ppat.1008932.ref024) 2018; 14
A Palencia (ppat.1008932.ref018) 2017; 9
S. Michaeli (ppat.1008932.ref023) 2011; 6
V Coustou (ppat.1008932.ref035) 2010; 4
S Wyllie (ppat.1008932.ref048) 2016; 12
G Jung (ppat.1008932.ref030) 1998; 124
T Akama (ppat.1008932.ref013) 2018; 28
CT Liu (ppat.1008932.ref004) 2014; 22
D Ding (ppat.1008932.ref007) 2010; 1
E Rico (ppat.1008932.ref027) 2018; 8
Y Liao (ppat.1008932.ref039) 2013; 30
L Glover (ppat.1008932.ref043) 2015; 10
SJ Remington (ppat.1008932.ref033) 1994; 244
C Proudfoot (ppat.1008932.ref040) 2005; 33
J. O'Neill (ppat.1008932.ref001) 2016
EL Ivanov (ppat.1008932.ref028) 1996; 142
FL Rock (ppat.1008932.ref019) 2007; 316
P Buscher (ppat.1008932.ref011) 2017; 390
RJ Wall (ppat.1008932.ref015) 2018; 115
JA Endrizzi (ppat.1008932.ref029) 1994; 33
Y Xia (ppat.1008932.ref021) 2011; 21
NG Jones (ppat.1008932.ref045) 2014; 10
DC Jones (ppat.1008932.ref016) 2015; 9
D Begolo (ppat.1008932.ref014) 2018; 14
G Schumann Burkard (ppat.1008932.ref041) 2011; 175
F Parussini (ppat.1008932.ref031) 2003; 131
K Van Bocxlaer (ppat.1008932.ref006) 2019; 11
B Langmead (ppat.1008932.ref037) 2012; 9
MP Barrett (ppat.1008932.ref012) 2018; 12
RT Jacobs (ppat.1008932.ref009) 2011; 5
KMV Sindhe (ppat.1008932.ref025) 2020; 11
E Sonoiki (ppat.1008932.ref017) 2017; 8
BM Swallow (ppat.1008932.ref002) 2000
H Li (ppat.1008932.ref038) 2009; 25
DJ Creek (ppat.1008932.ref046) 2012; 28
References_xml – volume: 51
  start-page: 83
  year: 1986
  ident: ppat.1008932.ref032
  article-title: Serine carboxypeptidases. A review
  publication-title: Carlsberg Res Commun
  doi: 10.1007/BF02907561
– volume: 4
  start-page: e618
  year: 2010
  ident: ppat.1008932.ref035
  article-title: Complete in vitro life cycle of Trypanosoma congolense: development of genetic tools
  publication-title: PLoS Negl Trop Dis
  doi: 10.1371/journal.pntd.0000618
– volume: 8
  start-page: 7960
  year: 2018
  ident: ppat.1008932.ref027
  article-title: Inducible high-efficiency CRISPR-Cas9-targeted gene editing and precision base editing in African trypanosomes
  publication-title: Sci Rep
  doi: 10.1038/s41598-018-26303-w
– volume: 33
  start-page: 6906
  year: 2005
  ident: ppat.1008932.ref040
  article-title: Distinct roles for two RAD51-related genes in Trypanosoma brucei antigenic variation
  publication-title: Nucleic Acids Res
  doi: 10.1093/nar/gki996
– volume: 390
  start-page: 2397
  year: 2017
  ident: ppat.1008932.ref011
  article-title: Human African trypanosomiasis
  publication-title: Lancet
  doi: 10.1016/S0140-6736(17)31510-6
– volume: 1824
  start-page: 195
  year: 2012
  ident: ppat.1008932.ref034
  article-title: The peptidases of Trypanosoma cruzi: digestive enzymes, virulence factors, and mediators of autophagy and programmed cell death
  publication-title: Biochim Biophys Acta
  doi: 10.1016/j.bbapap.2011.05.011
– volume: 6
  start-page: 459
  year: 2011
  ident: ppat.1008932.ref023
  article-title: Trans-splicing in trypanosomes: machinery and its impact on the parasite transcriptome
  publication-title: Future Microbiol
  doi: 10.2217/fmb.11.20
– volume: 33
  start-page: 4007
  year: 2017
  ident: ppat.1008932.ref047
  article-title: PiMP my metabolome: an integrated, web-based tool for LC-MS metabolomics data
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btx499
– volume: 143
  start-page: 1862
  year: 2016
  ident: ppat.1008932.ref003
  article-title: The animal trypanosomiases and their chemotherapy: a review
  publication-title: Parasitology
  doi: 10.1017/S0031182016001268
– volume: 40
  start-page: D343
  year: 2012
  ident: ppat.1008932.ref042
  article-title: MEROPS: the database of proteolytic enzymes, their substrates and inhibitors
  publication-title: Nucleic Acids Res
  doi: 10.1093/nar/gkr987
– volume: 1
  start-page: 165
  year: 2010
  ident: ppat.1008932.ref007
  article-title: Discovery of novel benzoxaborole-based potent antitrypanosomal agents
  publication-title: ACS Med Chem Lett
  doi: 10.1021/ml100013s
– volume: 175
  start-page: 91
  year: 2011
  ident: ppat.1008932.ref041
  article-title: Genome-wide RNAi screens in bloodstream form trypanosomes identify drug transporters
  publication-title: Mol Biochem Parasitol
  doi: 10.1016/j.molbiopara.2010.09.002
– volume: 28
  start-page: 1048
  year: 2012
  ident: ppat.1008932.ref046
  article-title: IDEOM: an Excel interface for analysis of LC-MS-based metabolomics data
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/bts069
– volume: 7
  start-page: 13
  year: 2014
  ident: ppat.1008932.ref008
  article-title: From the test tube to the treatment room: fundamentals of boron-containing compounds and their relevance to dermatology
  publication-title: J Clin Aesthet Dermatol
– volume: 10
  start-page: e1003886
  year: 2014
  ident: ppat.1008932.ref045
  article-title: Regulators of Trypanosoma brucei cell cycle progression and differentiation identified using a kinome-wide RNAi screen
  publication-title: PLoS Pathog
  doi: 10.1371/journal.ppat.1003886
– volume: 22
  start-page: 4462
  year: 2014
  ident: ppat.1008932.ref004
  article-title: The unique chemistry of benzoxaboroles: current and emerging applications in biotechnology and therapeutic treatments
  publication-title: Bioorg Med Chem
  doi: 10.1016/j.bmc.2014.04.065
– volume: 28
  start-page: 464
  year: 2012
  ident: ppat.1008932.ref044
  article-title: Artemis: an integrated platform for visualization and analysis of high-throughput sequence-based experimental data
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btr703
– volume: 142
  start-page: 693
  year: 1996
  ident: ppat.1008932.ref028
  article-title: Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae
  publication-title: Genetics
  doi: 10.1093/genetics/142.3.693
– year: 2016
  ident: ppat.1008932.ref001
  publication-title: Tackling drug-resistant infections globally: final report and recommendations—The review on antimicrobial resistance
– volume: 57
  start-page: 1394
  year: 2013
  ident: ppat.1008932.ref020
  article-title: Discovery of a novel class of boron-based antibacterials with activity against gram-negative bacteria
  publication-title: Antimicrob Agents Chemother
  doi: 10.1128/AAC.02058-12
– volume: 57
  start-page: 2768
  year: 2013
  ident: ppat.1008932.ref036
  article-title: Metabolomics guides rational development of a simplified cell culture medium for drug screening against Trypanosoma brucei
  publication-title: Antimicrob Agents Chemother
  doi: 10.1128/AAC.00044-13
– volume: 12
  start-page: e0006925
  year: 2018
  ident: ppat.1008932.ref012
  article-title: The elimination of human African trypanosomiasis is in sight: report from the third WHO stakeholders meeting on elimination of gambiense human African trypanosomiasis
  publication-title: PLoS Negl Trop Dis
  doi: 10.1371/journal.pntd.0006925
– volume: 12
  start-page: e0006450
  year: 2018
  ident: ppat.1008932.ref022
  article-title: Benzoxaborole treatment perturbs S-adenosyl-L-methionine metabolism in Trypanosoma brucei
  publication-title: PLoS Negl Trop Dis
  doi: 10.1371/journal.pntd.0006450
– volume: 11
  start-page: 129
  year: 2019
  ident: ppat.1008932.ref006
  article-title: Novel benzoxaborole, nitroimidazole and aminopyrazoles with activity against experimental cutaneous leishmaniasis
  publication-title: Int J Parasitol Drugs Drug Resist
  doi: 10.1016/j.ijpddr.2019.02.002
– volume: 5
  start-page: e1151
  year: 2011
  ident: ppat.1008932.ref009
  article-title: SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human African trypanosomiasis
  publication-title: PLoS Negl Trop Dis
  doi: 10.1371/journal.pntd.0001151
– volume: 131
  start-page: 11
  year: 2003
  ident: ppat.1008932.ref031
  article-title: Characterization of a lysosomal serine carboxypeptidase from Trypanosoma cruzi
  publication-title: Mol Biochem Parasitol
  doi: 10.1016/S0166-6851(03)00175-0
– volume: 10
  start-page: 106
  year: 2015
  ident: ppat.1008932.ref043
  article-title: Genome-scale RNAi screens for high-throughput phenotyping in bloodstream-form African trypanosomes
  publication-title: Nat Protoc
  doi: 10.1038/nprot.2015.005
– volume: 14
  start-page: e1007315
  year: 2018
  ident: ppat.1008932.ref014
  article-title: The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing
  publication-title: PLoS pathog
  doi: 10.1371/journal.ppat.1007315
– volume: 28
  start-page: 6
  year: 2018
  ident: ppat.1008932.ref013
  article-title: Identification of a 4-fluorobenzyl l-valinate amide benzoxaborole (AN11736) as a potential development candidate for the treatment of Animal African Trypanosomiasis (AAT)
  publication-title: Bioorg Med Chem Lett
  doi: 10.1016/j.bmcl.2017.11.028
– volume: 115
  start-page: 9616
  year: 2018
  ident: ppat.1008932.ref015
  article-title: Clinical and veterinary trypanocidal benzoxaboroles target CPSF3
  publication-title: Proc Natl Acad Sci USA
  doi: 10.1073/pnas.1807915115
– volume: 8
  start-page: 14574
  year: 2017
  ident: ppat.1008932.ref017
  article-title: A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue.
  publication-title: Nat Commun
  doi: 10.1038/ncomms14574
– volume: 28
  start-page: 493
  year: 2018
  ident: ppat.1008932.ref005
  article-title: Benzoxaborole compounds for therapeutic uses: a patent review (2010–2018)
  publication-title: Expert Opin Ther Pat
  doi: 10.1080/13543776.2018.1473379
– volume: 316
  start-page: 1759
  year: 2007
  ident: ppat.1008932.ref019
  article-title: An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site
  publication-title: Science
  doi: 10.1126/science.1142189
– volume: 30
  start-page: 923
  year: 2013
  ident: ppat.1008932.ref039
  article-title: featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btt656
– volume-title: Impacts of trypanosomiasis on African agriculture. PAAT Technical and Scientific Series 2
  year: 2000
  ident: ppat.1008932.ref002
– volume: 9
  start-page: e0004299
  year: 2015
  ident: ppat.1008932.ref016
  article-title: Genomic and proteomic studies on the mode of action of oxaboroles against the African trypanosome
  publication-title: PLoS Negl Trop Dis
  doi: 10.1371/journal.pntd.0004299
– volume: 21
  start-page: 2533
  year: 2011
  ident: ppat.1008932.ref021
  article-title: Synthesis and SAR of novel benzoxaboroles as a new class of beta-lactamase inhibitors
  publication-title: Bioorg Med Chem Lett
  doi: 10.1016/j.bmcl.2011.02.024
– volume: 14
  start-page: e1006850
  year: 2018
  ident: ppat.1008932.ref024
  article-title: Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles
  publication-title: PLoS Pathog.
  doi: 10.1371/journal.ppat.1006850
– volume: 33
  start-page: 11106
  year: 1994
  ident: ppat.1008932.ref029
  article-title: 2.8-Å structure of yeast serine carboxypeptidase
  publication-title: Biochemistry
  doi: 10.1021/bi00203a007
– volume: 3
  start-page: 1259
  year: 2011
  ident: ppat.1008932.ref010
  article-title: Benzoxaboroles: a new class of potential drugs for human African trypanosomiasis
  publication-title: Future Med Chem
  doi: 10.4155/fmc.11.80
– volume: 25
  start-page: 2078
  year: 2009
  ident: ppat.1008932.ref038
  article-title: The Sequence Alignment/Map format and SAMtools
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btp352
– volume: 12
  start-page: e1005971
  year: 2016
  ident: ppat.1008932.ref048
  article-title: Activation of bicyclic nitro-drugs by a novel nitroreductase (NTR2) in Leishmania
  publication-title: PLoS Pathog
  doi: 10.1371/journal.ppat.1005971
– volume: 244
  start-page: 231
  year: 1994
  ident: ppat.1008932.ref033
  article-title: Carboxypeptidases C and D
  publication-title: Methods Enzymol
  doi: 10.1016/0076-6879(94)44020-4
– volume: 9
  start-page: 357
  year: 2012
  ident: ppat.1008932.ref037
  article-title: Fast gapped-read alignment with Bowtie 2
  publication-title: Nat Methods
  doi: 10.1038/nmeth.1923
– volume: 124
  start-page: 446
  year: 1998
  ident: ppat.1008932.ref030
  article-title: Proton-relay system of carboxypeptidase Y as a sole catalytic site: studies on mutagenic replacement of His 397
  publication-title: J Biochem
  doi: 10.1093/oxfordjournals.jbchem.a022133
– volume: 9
  start-page: 385
  year: 2017
  ident: ppat.1008932.ref018
  article-title: Targeting Toxoplasma gondii CPSF3 as a new approach to control toxoplasmosis
  publication-title: EMBO Mol Med
  doi: 10.15252/emmm.201607370
– volume: 482
  start-page: 232
  year: 2012
  ident: ppat.1008932.ref026
  article-title: High-throughput decoding of antitrypanosomal drug efficacy and resistance
  publication-title: Nature
  doi: 10.1038/nature10771
– volume: 11
  start-page: e02640
  year: 2020
  ident: ppat.1008932.ref025
  article-title: Plasmodium falciparum resistance to a lead benzoxaborole due to blocked compound activation and altered ubiquitination or sumoylation
  publication-title: mBio
SSID ssj0041316
Score 2.4507565
Snippet Livestock diseases caused by Trypanosoma congolense , T . vivax and T . brucei , collectively known as nagana, are responsible for billions of dollars in lost...
Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food...
In Trypanosoma brucei treated with acoziborole, metabolomics experiments revealed a profound change in methionine metabolism [22], that may relate to RNA...
SourceID plos
doaj
pubmedcentral
proquest
gale
pubmed
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage e1008932
SubjectTerms Aldehyde dehydrogenase
Aldehydes
Analysis
Animals
Biology and Life Sciences
Boron Compounds - metabolism
Carboxylic Acids - metabolism
Carboxypeptidase
Carboxypeptidases - metabolism
Chemical compounds
Chemical properties
Chromosome 10
Chromosomes
Cloning
Dosage and administration
Drug dosages
Drug Resistance
Drug therapy
Drugs
Enzyme activation
Female
Forecasts and trends
Gene sequencing
Genes
Genomes
Identification and classification
Infectious diseases
Influence
Livestock
Metabolism
Metabolomics
Methionine
Methylation
Mice
Nucleotide sequence
Parasitemia - veterinary
Parasites
Peptidase
Peptidases
Peptides
Physical Sciences
Prodrugs
Prodrugs - metabolism
Proteases
Protozoan Proteins - metabolism
Research and Analysis Methods
RNA processing
Serine
Serine carboxypeptidase
Splicing
Synteny
Trypanocidal Agents - metabolism
Trypanosoma
Trypanosoma brucei brucei - drug effects
Trypanosoma brucei brucei - enzymology
Trypanosoma congolense - drug effects
Trypanosoma congolense - enzymology
Trypanosoma vivax - drug effects
Trypanosoma vivax - enzymology
Trypanosomiasis, African - drug therapy
Trypanosomiasis, African - parasitology
Trypanosomiasis, African - veterinary
Valine - analogs & derivatives
Valine - metabolism
Veterinary research
Whole genome sequencing
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9QwELbQSkhcEO8GCgoIiZNpHDv2-lgQpSDRA1DUm-VnQaqSaLOL2v56ZpJs1KCiXrjG40ieGXs-JzPfEPLaWcGF9IxqFSsKiHhJrUyCRu3wP1_hUoXFyV-O5OGx-HxSnVxp9YU5YQM98KC4PVsFZq0XtkhBKFdqqXS0QkkXIJKlvswXYt72MjWcwXAy901PsSkOVVzKsWiOK7Y32uht21qkjy4gYJezoNRz908n9KI9a7rr4OffWZRXwtLBPXJ3xJP5_rCO--RWrB-Q20OHyYuH5OMPTHfpa27z9eoCtj4YI8AEF-vL5hw9ABmdcruKeYsJLgGiGsVih98AQkOO5-tqc9o9IscHH76_P6Rj7wTqIeKuaQrJaQ33jeRilSKLNvkEKnNFTEseImMWoJn1NnGnrEiFt1LFMmrrSoakbY_Jom7quENyEcCgQVeRhQr7lWlAuhDotQ9w_QGAlBG-VZ7xI7E49rc4M_3fMgUXjEEXBlVuRpVnhE6z2oFY4wb5d2iXSRZpsfsH4CxmdBZzk7Nk5BVa1SDxRY2ZNad203Xm07cjsw_QDLAiX6p_Cn2dCb0ZhVIDi_V2rGYAlSGh1kxydyYJ29fPhnfQw7Zr7kzZc_5rwMUwc-t11w-_nIbxpZgtV8dmgzJwi0TkXWTkyeCkk944Z4ItZZURNXPfmWLnI_Wvnz3vuAI0ygr-9H9Y4hm5U-KXC_xAz3fJYr3axOcA79buRb-T_wDMeE9q
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: ProQuest Central
  dbid: BENPR
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV1Lb9QwELZgKyQuFe8GCgoIiZNpHCdxfEItailIrFChqLfIzwWpStLNLqL8emayTiCowHU9jtbj8cxne_wNIc-1ynhWGEalcDkFRFxSVfiMOqnxni_RPsfHye_nxfFp9u4sPwsHbl1Iqxx8Yu-obWPwjHwv7anQJcCFV-0FxapReLsaSmhcJ1vggst8RrYODucfTgZfDB66L36KxXGo4EURHs9xwfbCXL1sW4U00gkE7nQSnHoO_9FTz9rzprsKhv6ZTflbeDq6RbYDroz3N4Zwm1xz9R1yY1Np8vIuefMZ0176t7fxankJLgAmxUIH7eofzXe0BGR2itXSxS0muliIbhQfPXwDMGpj9LPL9aK7R06PDj-9PqahhgI1EHlX1FuvpYR9h9cu94455Y3XNtGJ8yW3jjEFEE0Z5bkWKvOJUYVwqZNKpwzJ2-6TWd3UbofEmYWJtTJ3zOZYt0wC4oWAL42FbRAApYjwQXmVCQTjWOfivOpvzQRsNDa6qFDlVVB5ROjYq90QbPxH_gDnZZRFeuz-h2a5qMJqq1RumVImU4m3mdCpLIR0KhMFjJzlvozIM5zVCgkwasywWah111VvP86rfYBogBl5Kf4qdDIRehGEfAODNSq8agCVIbHWRHJ3IgnL2Eyad9DChjF31S-Dh56D1V3d_HRsxo9i1lztmjXKwG4SEXgSkQcbIx31xjnLWFnkERET850odtpSf_3S848LQKUs4Q___bcekZspnk3gETzfJbPVcu0eA4Bb6Sdhlf4EvHdHjQ
  priority: 102
  providerName: ProQuest
Title Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs
URI https://www.ncbi.nlm.nih.gov/pubmed/33141865
https://www.proquest.com/docview/2479469522
https://www.proquest.com/docview/2457650880
https://pubmed.ncbi.nlm.nih.gov/PMC7710103
https://doaj.org/article/a5d1aac4a0fd47b29679ea476bd015f8
http://dx.doi.org/10.1371/journal.ppat.1008932
Volume 16
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV3db9MwELdGJyReEN_LGFVASDxlihMnjh8Q2tDGQFqFBkV9i-zYLkhVEpJ2WvnrucuXCOrgtT5H9fl89zv7Pgh5rSQLWZxRT3ATeYCIE0_GlnlGKHzn85WNMDn5chZfzNmnRbTYI33P1o6B9U7XDvtJzavV8c3P7Ts48G-brg2c9pOOy1JiQWgfTDAo5X2wTTHK-SUb3hVAYzfNULFZjsfDOO6S6W77yshYNTX9B809KVdFvQuW_h1d-Ye5On9A7nc40z1pBeMh2TP5I3K37Ty5fUw-fMMwmCYX111XW1AJsEkaJiiT_ypuUDKw0pMrK-OWGPiiwdp5mARxDeBUu6h3q82yfkLm52df3194XU8FLwNLvPastkoI8EOsMpE11EibWaV95RubhNpQKgGyyUzaUHHJrJ_JmJvACKkCisXcnpJJXuTmgLhMw0ZrERmqI-xjJgABAwAQmQa3CICTQ8KeeWnWFRzHvhertHlF4-B4tLxIkeVpx3KHeMOssi248R_6U9yXgRbLZTc_FNUy7U5fKiNNpcyY9K1mXAUi5sJIxmNYOY1s4pBXuKspFsTIMeJmKTd1nX78MktPALIBhgwTfivR1YjoTUdkC1hsJrssB2AZFtoaUR6NKOFYZ6PhA5Swfs11GjS9AATgZZjZS93u4ZfDMH4Uo-hyU2yQBrxLROS-Q561QjrwLQwpo0kcOYSPxHfE2PFI_uN7U4-cA0qlfnj477_1nNwL8K4Cr-TDIzJZVxvzAgDdWk3JHb7gU7J_ejb7fDVtrkWmzbn9DRH8T3M
linkProvider Scholars Portal
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELbKVgguiHe3FAgIxMk0jpN4fUCohZZd2q5QaVFvwY7tpVKVhM0usPwofiMzeSwEFTj1Go-teDye-WzPg5AnWoU8jFNGpbARBUQ8oCp2IbVS4zufr12EwckH43h4HL49iU5WyI82FgbdKludWClqk6d4R74ZVKnQJcCFl8VnilWj8HW1LaFRi8WeXXyFI1v5YvQa1vdpEOzuHL0a0qaqAE3BFs2oM05LCUjcaRs5y6xyqdPG1751A24sYwpAi0qV41qo0PmpioUNrFQ6YJjODMa9RFYBZkjYRavbO-N3h63uB4tQFVvFYjxU8DhugvW4YJuNbDwvCoVpq30ACkHHGFY1A5aWoVec5eV5sPdP783fzOHudXKtwbHeVi14N8iKzW6Sy3Vly8Ut8uYDutlUsb7ebLoAlQNCYKCDttn3_BtKHmaS8tTUegU61hiwphSDLL4A-DUe6vXpfFLeJscXwt07pJflmV0jXmhAkIyMLDMR1kmTgLABYMjUwLELgFmf8JZ5SdokNMe6GmdJ9Uon4GBT8yJBlicNy_uELnsVdUKP_9Bv47osaTEdd_Uhn06SZncnKjJMqTRUvjOh0IGMhbQqFDHMnEVu0CePcVUTTLiRoUfPRM3LMhm9HydbAAkBo_KB-CvRYYfoWUPkcphsqpooCmAZJvLqUG50KEFtpJ3mNZSwds5l8muDQc9W6s5vfrRsxkHRSy-z-Rxp4PSKiN_vk7u1kC75xjkL2SCO-kR0xLfD2G5LdvqpyncuAAUzn6__-7cekivDo4P9ZH803rtHrgZ4L4LX_3yD9GbTub0P4HGmHzQ71iMfL1pJ_ARzNYhE
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3db9MwELdGJxAviO8FBgQE4ik0jpM4eUBoYysrg2oabNpbsGO7IE1JaFqg_Gn8ddwlTiFowNNe63PUnH---zm-D0IeSxGyMM6pl3IdecCIE0_EJvR0KvGez5cmwuTkt5N47yh8fRKdrJEfXS4MhlV2NrEx1KrM8Rv5MGhKoadAF4bGhkUc7IxeVJ897CCFN61dO40WIvt6-RWOb_Xz8Q6s9ZMgGO2-f7nn2Q4DXg5-ae4ZZWSaAis3UkdGUy1MbqTypa9NwpSmVACBEbkwTHIRGj8XMdeBToUMKJY2g-deIOscvGIyIOvbu5ODw84PgHdoGq9iYx6Pszi2iXuM06HFybOqEljC2gfSEPQcY9M_YOUlBtVpWZ9Fgf-M5PzNNY6ukiuW07pbLQivkTVdXCcX2y6Xyxvk1TGG3DR5v-58tgTzA4BQMEHq4nv5DVGIVaVcMdNuhUE2CjyrhwkXX4AIKxdt_GwxrW-So3PR7i0yKMpCbxA3VAAqlUaaqgh7pqXAtoFspLmCIxiQNIewTnlZboubY4-N06y5seNwyGl1kaHKM6tyh3irWVVb3OM_8tu4LitZLM3d_FDOppnd6ZmIFBUiD4VvVMhlkMY81SLkMbw5jUzikEe4qhkW3ygQxlOxqOts_G6SbQE9BL7KEv5XocOe0FMrZEp42VzYjApQGRb16klu9iTBhOS94Q1EWPfOdfZrs8HMDnVnDz9cDeNDMWKv0OUCZeAki-zfd8jtFqQrvTFGQ5rEkUN4D749xfZHik8fm9rnHBgx9dmdf_-tB-QSGIfszXiyf5dcDvATCd4EsE0ymM8W-h7wyLm8bzesSz6ct434CWLejHA
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Veterinary+trypanocidal+benzoxaboroles+are+peptidase-activated+prodrugs&rft.jtitle=PLoS+pathogens&rft.au=Giordani%2C+Federica&rft.au=Paape%2C+Daniel&rft.au=Vincent%2C+Isabel+M&rft.au=Pountain%2C+Andrew+W&rft.date=2020-11-03&rft.pub=Public+Library+of+Science&rft.issn=1553-7366&rft.eissn=1553-7374&rft.volume=16&rft.issue=11&rft.spage=e1008932&rft_id=info:doi/10.1371%2Fjournal.ppat.1008932&rft.externalDBID=HAS_PDF_LINK
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1553-7374&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1553-7374&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1553-7374&client=summon