GlutaredoxinV1, Main, Exploration, bibRecord, 000477

An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.

Identifieur interne : 000477 ( Main/Exploration ); précédent : 000476; suivant : 000478

An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.

Auteurs : Ram B. Khattri [États-Unis] ; Daniel L. Morris [États-Unis] ; Caroline M. Davis [États-Unis] ; Stephanie M. Bilinovich [États-Unis] ; Andrew J. Caras [États-Unis] ; Matthew J. Panzner [États-Unis] ; Michael A. Debord [États-Unis] ; Thomas C. Leeper [États-Unis]

Source :

Molecules (Basel, Switzerland) [ 1420-3049 ] ; 2016.

RBID : pubmed:27438815

Descripteurs français

KwdFr :
- Bibliothèques de petites molécules (MeSH), Conformation moléculaire (MeSH), Découverte de médicament (méthodes), Humains (MeSH), Liaison aux protéines (MeSH), Ligands (MeSH), Protéines (antagonistes et inhibiteurs), Protéines (composition chimique), Relation structure-activité (MeSH), Simulation de docking moléculaire (MeSH), Simulation de dynamique moléculaire (MeSH), Sites de fixation (MeSH), Spectroscopie par résonance magnétique (MeSH), Évaluation préclinique de médicament (MeSH).
MESH :
- antagonistes et inhibiteurs : Protéines.
- composition chimique : Protéines.
- méthodes : Découverte de médicament.
- Bibliothèques de petites molécules, Conformation moléculaire, Humains, Liaison aux protéines, Ligands, Relation structure-activité, Simulation de docking moléculaire, Simulation de dynamique moléculaire, Sites de fixation, Spectroscopie par résonance magnétique, Évaluation préclinique de médicament.

English descriptors

KwdEn :
- Binding Sites (MeSH), Drug Discovery (methods), Drug Evaluation, Preclinical (MeSH), Humans (MeSH), Ligands (MeSH), Magnetic Resonance Spectroscopy (MeSH), Molecular Conformation (MeSH), Molecular Docking Simulation (MeSH), Molecular Dynamics Simulation (MeSH), Protein Binding (MeSH), Proteins (antagonists & inhibitors), Proteins (chemistry), Small Molecule Libraries (MeSH), Structure-Activity Relationship (MeSH).
MESH :
- chemical , antagonists & inhibitors : Proteins.
- chemical , chemistry : Proteins.
- chemical : Ligands, Small Molecule Libraries.
- methods : Drug Discovery.
- Binding Sites, Drug Evaluation, Preclinical, Humans, Magnetic Resonance Spectroscopy, Molecular Conformation, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding, Structure-Activity Relationship.

Abstract

Selective hits for the glutaredoxin ortholog of Brucella melitensis are determined using STD NMR and verified by trNOE and (15)N-HSQC titration. The most promising hit, RK207, was docked into the target molecule using a scoring function to compare simulated poses to experimental data. After elucidating possible poses, the hit was further optimized into the lead compound by extension with an electrophilic acrylamide warhead. We believe that focusing on selectivity in this early stage of drug discovery will limit cross-reactivity that might occur with the human ortholog as the lead compound is optimized. Kinetics studies revealed that lead compound 5 modified with an ester group results in higher reactivity than an acrylamide control; however, after modification this compound shows little selectivity for bacterial protein versus the human ortholog. In contrast, hydrolysis of compound 5 to the acid form results in a decrease in the activity of the compound. Together these results suggest that more optimization is warranted for this simple chemical scaffold, and opens the door for discovery of drugs targeted against glutaredoxin proteins-a heretofore untapped reservoir for antibiotic agents.

DOI: 10.3390/molecules21070846
PubMed: 27438815
PubMed Central: PMC6274284

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000427
to stream Main, to step Curation: 000427

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.</title>
<author><name sortKey="Khattri, Ram B" sort="Khattri, Ram B" uniqKey="Khattri R" first="Ram B" last="Khattri">Ram B. Khattri</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. rbk11@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Morris, Daniel L" sort="Morris, Daniel L" uniqKey="Morris D" first="Daniel L" last="Morris">Daniel L. Morris</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. dlm93@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Davis, Caroline M" sort="Davis, Caroline M" uniqKey="Davis C" first="Caroline M" last="Davis">Caroline M. Davis</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. cmd71@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bilinovich, Stephanie M" sort="Bilinovich, Stephanie M" uniqKey="Bilinovich S" first="Stephanie M" last="Bilinovich">Stephanie M. Bilinovich</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. sbilinovich@gmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Caras, Andrew J" sort="Caras, Andrew J" uniqKey="Caras A" first="Andrew J" last="Caras">Andrew J. Caras</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. ajc127@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Panzner, Matthew J" sort="Panzner, Matthew J" uniqKey="Panzner M" first="Matthew J" last="Panzner">Matthew J. Panzner</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. mjp9@uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Debord, Michael A" sort="Debord, Michael A" uniqKey="Debord M" first="Michael A" last="Debord">Michael A. Debord</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. mad151@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Leeper, Thomas C" sort="Leeper, Thomas C" uniqKey="Leeper T" first="Thomas C" last="Leeper">Thomas C. Leeper</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. tleeper@gmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2016">2016</date>
<idno type="RBID">pubmed:27438815</idno>
<idno type="pmid">27438815</idno>
<idno type="doi">10.3390/molecules21070846</idno>
<idno type="pmc">PMC6274284</idno>
<idno type="wicri:Area/Main/Corpus">000427</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000427</idno>
<idno type="wicri:Area/Main/Curation">000427</idno>
<idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000427</idno>
<idno type="wicri:Area/Main/Exploration">000427</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.</title>
<author><name sortKey="Khattri, Ram B" sort="Khattri, Ram B" uniqKey="Khattri R" first="Ram B" last="Khattri">Ram B. Khattri</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. rbk11@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Morris, Daniel L" sort="Morris, Daniel L" uniqKey="Morris D" first="Daniel L" last="Morris">Daniel L. Morris</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. dlm93@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Davis, Caroline M" sort="Davis, Caroline M" uniqKey="Davis C" first="Caroline M" last="Davis">Caroline M. Davis</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. cmd71@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bilinovich, Stephanie M" sort="Bilinovich, Stephanie M" uniqKey="Bilinovich S" first="Stephanie M" last="Bilinovich">Stephanie M. Bilinovich</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. sbilinovich@gmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Caras, Andrew J" sort="Caras, Andrew J" uniqKey="Caras A" first="Andrew J" last="Caras">Andrew J. Caras</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. ajc127@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Panzner, Matthew J" sort="Panzner, Matthew J" uniqKey="Panzner M" first="Matthew J" last="Panzner">Matthew J. Panzner</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. mjp9@uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Debord, Michael A" sort="Debord, Michael A" uniqKey="Debord M" first="Michael A" last="Debord">Michael A. Debord</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. mad151@zips.uakron.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Leeper, Thomas C" sort="Leeper, Thomas C" uniqKey="Leeper T" first="Thomas C" last="Leeper">Thomas C. Leeper</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. tleeper@gmail.com.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325</wicri:regionArea>
<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Molecules (Basel, Switzerland)</title>
<idno type="eISSN">1420-3049</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding Sites (MeSH)</term>
<term>Drug Discovery (methods)</term>
<term>Drug Evaluation, Preclinical (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Ligands (MeSH)</term>
<term>Magnetic Resonance Spectroscopy (MeSH)</term>
<term>Molecular Conformation (MeSH)</term>
<term>Molecular Docking Simulation (MeSH)</term>
<term>Molecular Dynamics Simulation (MeSH)</term>
<term>Protein Binding (MeSH)</term>
<term>Proteins (antagonists & inhibitors)</term>
<term>Proteins (chemistry)</term>
<term>Small Molecule Libraries (MeSH)</term>
<term>Structure-Activity Relationship (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Bibliothèques de petites molécules (MeSH)</term>
<term>Conformation moléculaire (MeSH)</term>
<term>Découverte de médicament (méthodes)</term>
<term>Humains (MeSH)</term>
<term>Liaison aux protéines (MeSH)</term>
<term>Ligands (MeSH)</term>
<term>Protéines (antagonistes et inhibiteurs)</term>
<term>Protéines (composition chimique)</term>
<term>Relation structure-activité (MeSH)</term>
<term>Simulation de docking moléculaire (MeSH)</term>
<term>Simulation de dynamique moléculaire (MeSH)</term>
<term>Sites de fixation (MeSH)</term>
<term>Spectroscopie par résonance magnétique (MeSH)</term>
<term>Évaluation préclinique de médicament (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Ligands</term>
<term>Small Molecule Libraries</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Protéines</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Drug Discovery</term>
</keywords>
<keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Découverte de médicament</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term>
<term>Drug Evaluation, Preclinical</term>
<term>Humans</term>
<term>Magnetic Resonance Spectroscopy</term>
<term>Molecular Conformation</term>
<term>Molecular Docking Simulation</term>
<term>Molecular Dynamics Simulation</term>
<term>Protein Binding</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Bibliothèques de petites molécules</term>
<term>Conformation moléculaire</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Ligands</term>
<term>Relation structure-activité</term>
<term>Simulation de docking moléculaire</term>
<term>Simulation de dynamique moléculaire</term>
<term>Sites de fixation</term>
<term>Spectroscopie par résonance magnétique</term>
<term>Évaluation préclinique de médicament</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Selective hits for the glutaredoxin ortholog of Brucella melitensis are determined using STD NMR and verified by trNOE and (15)N-HSQC titration. The most promising hit, RK207, was docked into the target molecule using a scoring function to compare simulated poses to experimental data. After elucidating possible poses, the hit was further optimized into the lead compound by extension with an electrophilic acrylamide warhead. We believe that focusing on selectivity in this early stage of drug discovery will limit cross-reactivity that might occur with the human ortholog as the lead compound is optimized. Kinetics studies revealed that lead compound 5 modified with an ester group results in higher reactivity than an acrylamide control; however, after modification this compound shows little selectivity for bacterial protein versus the human ortholog. In contrast, hydrolysis of compound 5 to the acid form results in a decrease in the activity of the compound. Together these results suggest that more optimization is warranted for this simple chemical scaffold, and opens the door for discovery of drugs targeted against glutaredoxin proteins-a heretofore untapped reservoir for antibiotic agents. </div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27438815</PMID>
<DateCompleted><Year>2017</Year>
<Month>04</Month>
<Day>18</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>02</Month>
<Day>25</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1420-3049</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>21</Volume>
<Issue>7</Issue>
<PubDate><Year>2016</Year>
<Month>Jul</Month>
<Day>16</Day>
</PubDate>
</JournalIssue>
<Title>Molecules (Basel, Switzerland)</Title>
<ISOAbbreviation>Molecules</ISOAbbreviation>
</Journal>
<ArticleTitle>An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.</ArticleTitle>
<ELocationID EIdType="doi" ValidYN="Y">10.3390/molecules21070846</ELocationID>
<ELocationID EIdType="pii" ValidYN="Y">E846</ELocationID>
<Abstract><AbstractText>Selective hits for the glutaredoxin ortholog of Brucella melitensis are determined using STD NMR and verified by trNOE and (15)N-HSQC titration. The most promising hit, RK207, was docked into the target molecule using a scoring function to compare simulated poses to experimental data. After elucidating possible poses, the hit was further optimized into the lead compound by extension with an electrophilic acrylamide warhead. We believe that focusing on selectivity in this early stage of drug discovery will limit cross-reactivity that might occur with the human ortholog as the lead compound is optimized. Kinetics studies revealed that lead compound 5 modified with an ester group results in higher reactivity than an acrylamide control; however, after modification this compound shows little selectivity for bacterial protein versus the human ortholog. In contrast, hydrolysis of compound 5 to the acid form results in a decrease in the activity of the compound. Together these results suggest that more optimization is warranted for this simple chemical scaffold, and opens the door for discovery of drugs targeted against glutaredoxin proteins-a heretofore untapped reservoir for antibiotic agents. </AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Khattri</LastName>
<ForeName>Ram B</ForeName>
<Initials>RB</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. rbk11@zips.uakron.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Morris</LastName>
<ForeName>Daniel L</ForeName>
<Initials>DL</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. dlm93@zips.uakron.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Davis</LastName>
<ForeName>Caroline M</ForeName>
<Initials>CM</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. cmd71@zips.uakron.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bilinovich</LastName>
<ForeName>Stephanie M</ForeName>
<Initials>SM</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA. sbilinovich@gmail.com.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Caras</LastName>
<ForeName>Andrew J</ForeName>
<Initials>AJ</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. ajc127@zips.uakron.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Panzner</LastName>
<ForeName>Matthew J</ForeName>
<Initials>MJ</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. mjp9@uakron.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Debord</LastName>
<ForeName>Michael A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. mad151@zips.uakron.edu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Leeper</LastName>
<ForeName>Thomas C</ForeName>
<Initials>TC</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. tleeper@gmail.com.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>07</Month>
<Day>16</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Switzerland</Country>
<MedlineTA>Molecules</MedlineTA>
<NlmUniqueID>100964009</NlmUniqueID>
<ISSNLinking>1420-3049</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008024">Ligands</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011506">Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D054852">Small Molecule Libraries</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D001665" MajorTopicYN="N">Binding Sites</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055808" MajorTopicYN="Y">Drug Discovery</DescriptorName>
<QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004353" MajorTopicYN="N">Drug Evaluation, Preclinical</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008024" MajorTopicYN="Y">Ligands</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009682" MajorTopicYN="N">Magnetic Resonance Spectroscopy</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008968" MajorTopicYN="N">Molecular Conformation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D062105" MajorTopicYN="Y">Molecular Docking Simulation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D056004" MajorTopicYN="N">Molecular Dynamics Simulation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011506" MajorTopicYN="N">Proteins</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054852" MajorTopicYN="N">Small Molecule Libraries</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">FBDD</Keyword>
<Keyword MajorTopicYN="N">HSQC</Keyword>
<Keyword MajorTopicYN="N">STD</Keyword>
<Keyword MajorTopicYN="N">docking</Keyword>
<Keyword MajorTopicYN="N">glutaredoxin</Keyword>
<Keyword MajorTopicYN="N">ortholog</Keyword>
<Keyword MajorTopicYN="N">trNOE</Keyword>
<Keyword MajorTopicYN="N">warhead</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year>
<Month>03</Month>
<Day>29</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2016</Year>
<Month>06</Month>
<Day>20</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2016</Year>
<Month>06</Month>
<Day>22</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2016</Year>
<Month>7</Month>
<Day>21</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2016</Year>
<Month>7</Month>
<Day>22</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2017</Year>
<Month>4</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>epublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">27438815</ArticleId>
<ArticleId IdType="pii">molecules21070846</ArticleId>
<ArticleId IdType="doi">10.3390/molecules21070846</ArticleId>
<ArticleId IdType="pmc">PMC6274284</ArticleId>
</ArticleIdList>
<ReferenceList><Reference><Citation>J Med Chem. 2000 Sep 7;43(18):3443-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">10978192</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biomol NMR. 2000 Nov;18(3):189-98</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11142509</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11259830</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Am Chem Soc. 2001 Jun 27;123(25):6108-17</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11414845</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2001 Aug 16;44(17):2719-34</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11495584</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Semin Oncol. 2001 Oct;28(5 Suppl 16):80-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11706399</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Am Chem Soc. 2002 Oct 2;124(39):11758-63</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12296743</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Angew Chem Int Ed Engl. 2003 Feb 24;42(8):864-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12596167</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2004 May 6;47(10):2486-98</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15115392</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Annu Rev Biophys Biomol Struct. 2004;33:199-223</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15139811</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 1992 Mar 20;35(6):1067-75</Citation>
<ArticleIdList><ArticleId IdType="pubmed">1552501</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Bacteriol. 2005 Apr;187(8):2715-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15805518</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proc Natl Acad Sci U S A. 2005 May 24;102(21):7665-70</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15897464</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Lancet Infect Dis. 2006 Feb;6(2):91-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16439329</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biochemistry. 2006 Apr 18;45(15):4785-96</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16605247</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Am Chem Soc. 2006 Aug 2;128(30):9863-72</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16866544</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biomol NMR. 2007 Jun;38(2):139-50</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17457516</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Analyst. 2007 Jul;132(7):693-705</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17657909</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nucleic Acids Res. 2008 Jan;36(Database issue):D402-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17984079</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Acta Crystallogr A. 2008 Jan;64(Pt 1):112-22</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18156677</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 2008 Apr 4;283(14):8868-76</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18216016</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biochemistry. 2008 May 20;47(20):5481-92</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18412369</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2008 Jul 10;51(13):3661-80</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18457385</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Proteins. 2008 Aug 15;72(3):1077-83</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18473363</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Curr Opin Investig Drugs. 2008 Dec;9(12):1336-46</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19037840</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Infect Disord Drug Targets. 2009 Nov;9(5):493-506</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19594426</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2010 Mar 11;53(5):2038-50</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20151670</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2010 Mar 25;53(6):2577-88</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20192224</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biophys J. 2010 Jun 2;98(11):2682-91</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20513413</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2010 Jul 22;53(14):5256-66</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20575554</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Int J Antimicrob Agents. 2010 Nov;36 Suppl 1:S8-11</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20696557</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Chem Inf Model. 2010 Sep 27;50(9):1623-32</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20712341</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2011 Jan 13;54(1):3-25</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21077686</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2011 Mar 10;54(5):1347-55</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21322567</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Neurochem. 1990 Oct;55(4):1357-65</Citation>
<ArticleIdList><ArticleId IdType="pubmed">2144583</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Sep 1;67(Pt 9):1141-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21904064</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2012 Jan 12;55(1):268-79</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22098466</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Am Chem Soc. 2012 Feb 29;134(8):3792-803</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22280219</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2012 Mar 8;55(5):2251-64</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22280453</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Comput Aided Mol Des. 2012 Jun;26(6):775-86</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22566074</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2012 Jul 26;55(14):6243-62</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22621397</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Biochemistry. 2012 Oct 16;51(41):8189-207</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22966829</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Prog Nucl Magn Reson Spectrosc. 2013 Aug;73:1-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23962882</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Chem Rev. 2014 Feb 26;114(4):2313-42</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24313284</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Bioorg Med Chem Lett. 2014 Jan 1;24(1):33-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24314671</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2014 Jun 12;57(11):4969-74</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24870364</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ACS Med Chem Lett. 2012 Oct 04;3(12):1024-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24900424</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>ACS Med Chem Lett. 2012 Aug 09;3(9):731-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24900540</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Drug Discov Today Technol. 2006 Autumn;3(3):241-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24980524</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS One. 2014 Jul 15;9(7):e102300</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25025339</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Inorg Chem. 2014 Oct 6;53(19):10456-62</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25215611</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biomol NMR. 2014 Nov;60(2-3):147-56</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25256941</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 2014 Dec 26;57(24):10366-82</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25418070</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Bioinformatics. 2015 Apr 15;31(8):1325-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25505092</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Curr Protoc Protein Sci. 2015 Aug 03;81:17.18.1-24</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26237672</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Expert Opin Drug Discov. 2016;11(1):79-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26757171</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 1968 Apr 25;243(8):1942-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">5646485</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Arch Biochem Biophys. 1978 Jan 30;185(2):584-91</Citation>
<ArticleIdList><ArticleId IdType="pubmed">626512</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biol Chem. 1982 Jun 25;257(12):6686-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">7045093</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biomol NMR. 1994 May;4(3):341-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">8019141</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Biomol NMR. 1995 Nov;6(3):277-93</Citation>
<ArticleIdList><ArticleId IdType="pubmed">8520220</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Methods Enzymol. 1996;266:131-41</Citation>
<ArticleIdList><ArticleId IdType="pubmed">8743682</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 1996 Nov 29;274(5292):1531-4</Citation>
<ArticleIdList><ArticleId IdType="pubmed">8929414</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Med Chem. 1998 Jul 2;41(14):2579-87</Citation>
<ArticleIdList><ArticleId IdType="pubmed">9651162</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Mol Biol. 1998 Jul 24;280(4):687-701</Citation>
<ArticleIdList><ArticleId IdType="pubmed">9677297</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
<li>Ohio</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Ohio"><name sortKey="Khattri, Ram B" sort="Khattri, Ram B" uniqKey="Khattri R" first="Ram B" last="Khattri">Ram B. Khattri</name>
</region>
<name sortKey="Bilinovich, Stephanie M" sort="Bilinovich, Stephanie M" uniqKey="Bilinovich S" first="Stephanie M" last="Bilinovich">Stephanie M. Bilinovich</name>
<name sortKey="Caras, Andrew J" sort="Caras, Andrew J" uniqKey="Caras A" first="Andrew J" last="Caras">Andrew J. Caras</name>
<name sortKey="Davis, Caroline M" sort="Davis, Caroline M" uniqKey="Davis C" first="Caroline M" last="Davis">Caroline M. Davis</name>
<name sortKey="Debord, Michael A" sort="Debord, Michael A" uniqKey="Debord M" first="Michael A" last="Debord">Michael A. Debord</name>
<name sortKey="Leeper, Thomas C" sort="Leeper, Thomas C" uniqKey="Leeper T" first="Thomas C" last="Leeper">Thomas C. Leeper</name>
<name sortKey="Morris, Daniel L" sort="Morris, Daniel L" uniqKey="Morris D" first="Daniel L" last="Morris">Daniel L. Morris</name>
<name sortKey="Panzner, Matthew J" sort="Panzner, Matthew J" uniqKey="Panzner M" first="Matthew J" last="Panzner">Matthew J. Panzner</name>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Bois/explor/GlutaredoxinV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000477 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000477 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Bois
   |area=    GlutaredoxinV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:27438815
   |texte=   An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:27438815" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a GlutaredoxinV1

This area was generated with Dilib version V0.6.37.
Data generation: Wed Nov 18 15:13:42 2020. Site generation: Wed Nov 18 15:16:12 2020

	Serveur d'exploration sur la glutarédoxine
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration sur la glutarédoxine

An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.

An NMR-Guided Screening Method for Selective Fragment Docking and Synthesis of a Warhead Inhibitor.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki