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Identification of Peptide Antagonists to Thioredoxin Glutathione Reductase of Schistosoma japonicum.

Identifieur interne : 000251 ( Main/Exploration ); précédent : 000250; suivant : 000252

Identification of Peptide Antagonists to Thioredoxin Glutathione Reductase of Schistosoma japonicum.

Auteurs : Li-Jun Song [République populaire de Chine] ; Jia-Huang Li [République populaire de Chine] ; Xu-Ren Yin [République populaire de Chine] ; Wei Zhang [République populaire de Chine] ; Yi Jin [République populaire de Chine] ; Hong Gao [République populaire de Chine] ; Jie Wang [République populaire de Chine] ; Chuan-Xin Yu [République populaire de Chine] ; Zi-Chun Hua [République populaire de Chine]

Source :

RBID : pubmed:29967790

Descripteurs français

English descriptors

Abstract

Schistosomiasis is one of the world's major public health problems. Praziquantel is currently the only effective drug against schistosomiasis. As resistance of praziquantel has emerged in some endemic areas, development of new antischistosomal agents should be a high priority. In this study, a phage display peptide library was used for screening for peptide antagonists of thioredoxin glutathione reductase of Schistosoma japonicum (SjTGR), which has been identified as an alternative drug target. Three rounds of panning produced four different fusion phages. ELISA proved that all four phages could bind to SjTGR. One peptide, JIPDys1 (aa, WPHNWWPHFKVK), reduced enzyme activity of SjTGR by more than 50%. 2 μM of the synthesized peptide of JIPDys1 inhibited the activity of TrxR, GR, and Grx of SjTGR by 32.5%, 100%, and 100%, respectively. The IC50 values of the synthetic peptide JIPDys1 for TrxR, GR, and Grx were 3.67 μM, 0.11 μM, and 0.97 μM, respectively. Based on computer simulation, it appeared that JIPDys1 binds to the substrate binding sites of glutathione reductase (GR) and glutaredoxin (Grx). Our data show that the peptide, JIPDys1 (aa, WPHNWWPHFKVK), is a promising candidate to develop novel drugs against S. japonicum which acts by binding with SjTGR and reduces enzyme activity of SjTGR.

DOI: 10.1155/2018/9483928
PubMed: 29967790
PubMed Central: PMC6008883


Affiliations:


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Le document en format XML

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<name sortKey="Song, Li Jun" sort="Song, Li Jun" uniqKey="Song L" first="Li-Jun" last="Song">Li-Jun Song</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064</wicri:regionArea>
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<name sortKey="Jin, Yi" sort="Jin, Yi" uniqKey="Jin Y" first="Yi" last="Jin">Yi Jin</name>
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<nlm:affiliation>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064</wicri:regionArea>
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<name sortKey="Gao, Hong" sort="Gao, Hong" uniqKey="Gao H" first="Hong" last="Gao">Hong Gao</name>
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<nlm:affiliation>Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province 210008, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province 210008</wicri:regionArea>
<wicri:noRegion>Jiangsu Province 210008</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Wang, Jie" sort="Wang, Jie" uniqKey="Wang J" first="Jie" last="Wang">Jie Wang</name>
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<nlm:affiliation>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.</nlm:affiliation>
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<name sortKey="Yu, Chuan Xin" sort="Yu, Chuan Xin" uniqKey="Yu C" first="Chuan-Xin" last="Yu">Chuan-Xin Yu</name>
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<name sortKey="Hua, Zi Chun" sort="Hua, Zi Chun" uniqKey="Hua Z" first="Zi-Chun" last="Hua">Zi-Chun Hua</name>
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<nlm:affiliation>School of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu Province 210023, China.</nlm:affiliation>
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<wicri:regionArea>School of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu Province 210023</wicri:regionArea>
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<nlm:affiliation>Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, Jiangsu Province 213164, China.</nlm:affiliation>
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<wicri:regionArea>Shenzhen Research Institute of Nanjing University, Shenzhen, Guangdong Province 518057</wicri:regionArea>
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<title level="j">BioMed research international</title>
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<term>Animals (MeSH)</term>
<term>Computer Simulation (MeSH)</term>
<term>Glutathione Reductase (MeSH)</term>
<term>Multienzyme Complexes (antagonists & inhibitors)</term>
<term>NADH, NADPH Oxidoreductases (antagonists & inhibitors)</term>
<term>Peptides (MeSH)</term>
<term>Schistosoma japonicum (enzymology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux (MeSH)</term>
<term>Complexes multienzymatiques (antagonistes et inhibiteurs)</term>
<term>Glutathione reductase (MeSH)</term>
<term>NADH, NADPH oxidoreductases (antagonistes et inhibiteurs)</term>
<term>Peptides (MeSH)</term>
<term>Schistosoma japonicum (enzymologie)</term>
<term>Simulation numérique (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en">
<term>Multienzyme Complexes</term>
<term>NADH, NADPH Oxidoreductases</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en">
<term>Glutathione Reductase</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr">
<term>Complexes multienzymatiques</term>
<term>NADH, NADPH oxidoreductases</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr">
<term>Schistosoma japonicum</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en">
<term>Schistosoma japonicum</term>
</keywords>
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<term>Animals</term>
<term>Computer Simulation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Glutathione reductase</term>
<term>Peptides</term>
<term>Simulation numérique</term>
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<front>
<div type="abstract" xml:lang="en">Schistosomiasis is one of the world's major public health problems. Praziquantel is currently the only effective drug against schistosomiasis. As resistance of praziquantel has emerged in some endemic areas, development of new antischistosomal agents should be a high priority. In this study, a phage display peptide library was used for screening for peptide antagonists of thioredoxin glutathione reductase of
<i>Schistosoma japonicum</i>
(SjTGR), which has been identified as an alternative drug target. Three rounds of panning produced four different fusion phages. ELISA proved that all four phages could bind to SjTGR. One peptide, JIPDys1 (aa, WPHNWWPHFKVK), reduced enzyme activity of SjTGR by more than 50%. 2
<i>μ</i>
M of the synthesized peptide of JIPDys1 inhibited the activity of TrxR, GR, and Grx of SjTGR by 32.5%, 100%, and 100%, respectively. The IC
<sub>50</sub>
values of the synthetic peptide JIPDys1 for TrxR, GR, and Grx were 3.67
<i>μ</i>
M, 0.11
<i>μ</i>
M, and 0.97
<i>μ</i>
M, respectively. Based on computer simulation, it appeared that JIPDys1 binds to the substrate binding sites of glutathione reductase (GR) and glutaredoxin (Grx). Our data show that the peptide, JIPDys1 (aa, WPHNWWPHFKVK), is a promising candidate to develop novel drugs against
<i>S. japonicum</i>
which acts by binding with SjTGR and reduces enzyme activity of SjTGR.</div>
</front>
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<Day>07</Day>
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<Year>2019</Year>
<Month>01</Month>
<Day>07</Day>
</DateRevised>
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<Year>2018</Year>
</PubDate>
</JournalIssue>
<Title>BioMed research international</Title>
<ISOAbbreviation>Biomed Res Int</ISOAbbreviation>
</Journal>
<ArticleTitle>Identification of Peptide Antagonists to Thioredoxin Glutathione Reductase of
<i>Schistosoma japonicum</i>
.</ArticleTitle>
<Pagination>
<MedlinePgn>9483928</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1155/2018/9483928</ELocationID>
<Abstract>
<AbstractText>Schistosomiasis is one of the world's major public health problems. Praziquantel is currently the only effective drug against schistosomiasis. As resistance of praziquantel has emerged in some endemic areas, development of new antischistosomal agents should be a high priority. In this study, a phage display peptide library was used for screening for peptide antagonists of thioredoxin glutathione reductase of
<i>Schistosoma japonicum</i>
(SjTGR), which has been identified as an alternative drug target. Three rounds of panning produced four different fusion phages. ELISA proved that all four phages could bind to SjTGR. One peptide, JIPDys1 (aa, WPHNWWPHFKVK), reduced enzyme activity of SjTGR by more than 50%. 2
<i>μ</i>
M of the synthesized peptide of JIPDys1 inhibited the activity of TrxR, GR, and Grx of SjTGR by 32.5%, 100%, and 100%, respectively. The IC
<sub>50</sub>
values of the synthetic peptide JIPDys1 for TrxR, GR, and Grx were 3.67
<i>μ</i>
M, 0.11
<i>μ</i>
M, and 0.97
<i>μ</i>
M, respectively. Based on computer simulation, it appeared that JIPDys1 binds to the substrate binding sites of glutathione reductase (GR) and glutaredoxin (Grx). Our data show that the peptide, JIPDys1 (aa, WPHNWWPHFKVK), is a promising candidate to develop novel drugs against
<i>S. japonicum</i>
which acts by binding with SjTGR and reduces enzyme activity of SjTGR.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Song</LastName>
<ForeName>Li-Jun</ForeName>
<Initials>LJ</Initials>
<Identifier Source="ORCID">0000-0002-3897-5925</Identifier>
<AffiliationInfo>
<Affiliation>School of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu Province 210023, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Li</LastName>
<ForeName>Jia-Huang</ForeName>
<Initials>JH</Initials>
<Identifier Source="ORCID">0000-0003-3513-4159</Identifier>
<AffiliationInfo>
<Affiliation>School of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu Province 210023, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, Jiangsu Province 213164, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Yin</LastName>
<ForeName>Xu-Ren</ForeName>
<Initials>XR</Initials>
<Identifier Source="ORCID">0000-0003-3463-3378</Identifier>
<AffiliationInfo>
<Affiliation>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zhang</LastName>
<ForeName>Wei</ForeName>
<Initials>W</Initials>
<Identifier Source="ORCID">0000-0001-6791-5043</Identifier>
<AffiliationInfo>
<Affiliation>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Jin</LastName>
<ForeName>Yi</ForeName>
<Initials>Y</Initials>
<Identifier Source="ORCID">0000-0002-2103-9831</Identifier>
<AffiliationInfo>
<Affiliation>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Gao</LastName>
<ForeName>Hong</ForeName>
<Initials>H</Initials>
<Identifier Source="ORCID">0000-0002-8518-0033</Identifier>
<AffiliationInfo>
<Affiliation>Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province 210008, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Wang</LastName>
<ForeName>Jie</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">0000-0002-9453-9642</Identifier>
<AffiliationInfo>
<Affiliation>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Yu</LastName>
<ForeName>Chuan-Xin</ForeName>
<Initials>CX</Initials>
<Identifier Source="ORCID">0000-0002-6662-3847</Identifier>
<AffiliationInfo>
<Affiliation>Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province 214064, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Hua</LastName>
<ForeName>Zi-Chun</ForeName>
<Initials>ZC</Initials>
<Identifier Source="ORCID">0000-0002-4654-1801</Identifier>
<AffiliationInfo>
<Affiliation>School of Life Sciences and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu Province 210023, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, Jiangsu Province 213164, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Shenzhen Research Institute of Nanjing University, Shenzhen, Guangdong Province 518057, China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2018</Year>
<Month>06</Month>
<Day>05</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>United States</Country>
<MedlineTA>Biomed Res Int</MedlineTA>
<NlmUniqueID>101600173</NlmUniqueID>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D009097">Multienzyme Complexes</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D010455">Peptides</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 1.6.-</RegistryNumber>
<NameOfSubstance UI="D009247">NADH, NADPH Oxidoreductases</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 1.6.4.-</RegistryNumber>
<NameOfSubstance UI="C466433">thioredoxin glutathione reductase</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 1.8.1.7</RegistryNumber>
<NameOfSubstance UI="D005980">Glutathione Reductase</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D003198" MajorTopicYN="Y">Computer Simulation</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005980" MajorTopicYN="N">Glutathione Reductase</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009097" MajorTopicYN="N">Multienzyme Complexes</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D009247" MajorTopicYN="N">NADH, NADPH Oxidoreductases</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D010455" MajorTopicYN="Y">Peptides</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D012549" MajorTopicYN="N">Schistosoma japonicum</DescriptorName>
<QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData>
<History>
<PubMedPubDate PubStatus="received">
<Year>2018</Year>
<Month>01</Month>
<Day>16</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised">
<Year>2018</Year>
<Month>03</Month>
<Day>23</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2018</Year>
<Month>04</Month>
<Day>03</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2018</Year>
<Month>7</Month>
<Day>4</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2018</Year>
<Month>7</Month>
<Day>4</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2019</Year>
<Month>1</Month>
<Day>8</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>epublish</PublicationStatus>
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<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
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<country name="République populaire de Chine">
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<name sortKey="Song, Li Jun" sort="Song, Li Jun" uniqKey="Song L" first="Li-Jun" last="Song">Li-Jun Song</name>
</noRegion>
<name sortKey="Gao, Hong" sort="Gao, Hong" uniqKey="Gao H" first="Hong" last="Gao">Hong Gao</name>
<name sortKey="Hua, Zi Chun" sort="Hua, Zi Chun" uniqKey="Hua Z" first="Zi-Chun" last="Hua">Zi-Chun Hua</name>
<name sortKey="Hua, Zi Chun" sort="Hua, Zi Chun" uniqKey="Hua Z" first="Zi-Chun" last="Hua">Zi-Chun Hua</name>
<name sortKey="Hua, Zi Chun" sort="Hua, Zi Chun" uniqKey="Hua Z" first="Zi-Chun" last="Hua">Zi-Chun Hua</name>
<name sortKey="Jin, Yi" sort="Jin, Yi" uniqKey="Jin Y" first="Yi" last="Jin">Yi Jin</name>
<name sortKey="Li, Jia Huang" sort="Li, Jia Huang" uniqKey="Li J" first="Jia-Huang" last="Li">Jia-Huang Li</name>
<name sortKey="Li, Jia Huang" sort="Li, Jia Huang" uniqKey="Li J" first="Jia-Huang" last="Li">Jia-Huang Li</name>
<name sortKey="Song, Li Jun" sort="Song, Li Jun" uniqKey="Song L" first="Li-Jun" last="Song">Li-Jun Song</name>
<name sortKey="Wang, Jie" sort="Wang, Jie" uniqKey="Wang J" first="Jie" last="Wang">Jie Wang</name>
<name sortKey="Yin, Xu Ren" sort="Yin, Xu Ren" uniqKey="Yin X" first="Xu-Ren" last="Yin">Xu-Ren Yin</name>
<name sortKey="Yu, Chuan Xin" sort="Yu, Chuan Xin" uniqKey="Yu C" first="Chuan-Xin" last="Yu">Chuan-Xin Yu</name>
<name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name>
</country>
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