Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites
Identifieur interne : 000A39 ( Istex/Corpus ); précédent : 000A38; suivant : 000A40Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites
Auteurs : Alexander Berchanski ; Aviva LapidotSource :
- Journal of Molecular Modeling [ 1610-2940 ] ; 2009-03-01.
English descriptors
- KwdEn :
Abstract
Abstract: Aminoglycoside–arginine conjugates (AAC and APAC) are multi-target inhibitors of human immunodeficiency virus type-1 (HIV-1). Here, we predict new conjugates of neomycin with two arginine peptide chains binding at specific sites on neomycin [poly-arginine-neomycin-poly-arginine (PA-Neo-PA)]. The rationale for the design of such compounds is to separate two short arginine peptides with neomycin, which may extend the binding region of the CXC chemokine receptor type 4 (CXCR4). We used homology models of CXCR4 and unliganded envelope glycoprotein 120 (HIV-1IIIB gp120) and docked PA-Neo-PAs and APACs to these using a multistep docking procedure. The results indicate that PA-Neo-PAs spread over two negatively charged patches of CXCR4. PA-Neo-PA–CXCR4 complexes are energetically more favorable than AACs/APAC–CXCR4 complexes. Notably, our CXCR4 model and docking procedure can be applied to predict new compounds that are either inhibitors of gp120–CXCR4 binding without affecting stromal cell-derived factor 1α (SDF-1α) chemotaxis activity, or inhibitors of SDF-1α–CXCR4 binding resulting in an anti-metastasis effect. We also predict that PA-Neo-PAs and APACs can interfere with CD4–gp120 binding in unliganded conformation. Figure The r5-Neo-r5-CXCR4 complex. CXCR4 is shown in CPK representation. The negatively charged residues are shown in red and positively charged residues in blue. The r5-Neo-r5 is shown in stick representation, neomycin core is colored yellow and arginine moieties are colored magenta. Two negatively charged patches separated by neutral and positively charged residues are visible.
Url:
DOI: 10.1007/s00894-008-0401-1
Links to Exploration step
ISTEX:627E62E8DDCCBDD702E903064164A0C8357E4C4DLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites</title>
<author><name sortKey="Berchanski, Alexander" sort="Berchanski, Alexander" uniqKey="Berchanski A" first="Alexander" last="Berchanski">Alexander Berchanski</name>
<affiliation><mods:affiliation>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lapidot, Aviva" sort="Lapidot, Aviva" uniqKey="Lapidot A" first="Aviva" last="Lapidot">Aviva Lapidot</name>
<affiliation><mods:affiliation>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>E-mail: aviva.lapidot@weizmann.ac.il</mods:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">ISTEX</idno>
<idno type="RBID">ISTEX:627E62E8DDCCBDD702E903064164A0C8357E4C4D</idno>
<date when="2008" year="2008">2008</date>
<idno type="doi">10.1007/s00894-008-0401-1</idno>
<idno type="url">https://api.istex.fr/ark:/67375/VQC-WBV9ZP52-H/fulltext.pdf</idno>
<idno type="wicri:Area/Istex/Corpus">000A39</idno>
<idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000A39</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites</title>
<author><name sortKey="Berchanski, Alexander" sort="Berchanski, Alexander" uniqKey="Berchanski A" first="Alexander" last="Berchanski">Alexander Berchanski</name>
<affiliation><mods:affiliation>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lapidot, Aviva" sort="Lapidot, Aviva" uniqKey="Lapidot A" first="Aviva" last="Lapidot">Aviva Lapidot</name>
<affiliation><mods:affiliation>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>E-mail: aviva.lapidot@weizmann.ac.il</mods:affiliation>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j">Journal of Molecular Modeling</title>
<title level="j" type="sub">Computational Chemistry - Life Sciences - Advanced Materials - New Methods</title>
<title level="j" type="abbrev">J Mol Model</title>
<idno type="ISSN">1610-2940</idno>
<idno type="eISSN">0948-5023</idno>
<imprint><publisher>Springer-Verlag</publisher>
<pubPlace>Berlin/Heidelberg</pubPlace>
<date type="published" when="2009-03-01">2009-03-01</date>
<biblScope unit="volume">15</biblScope>
<biblScope unit="issue">3</biblScope>
<biblScope unit="page" from="281">281</biblScope>
<biblScope unit="page" to="294">294</biblScope>
</imprint>
<idno type="ISSN">1610-2940</idno>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><idno type="ISSN">1610-2940</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CXCR4/SDF-1α</term>
<term>HIV-1 entry inhibitors</term>
<term>Molecular modeling and docking</term>
<term>Poly-arginine aminoglycoside conjugates</term>
<term>Predicted compounds</term>
<term>gp120/CD4</term>
</keywords>
</textClass>
<langUsage><language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Abstract: Aminoglycoside–arginine conjugates (AAC and APAC) are multi-target inhibitors of human immunodeficiency virus type-1 (HIV-1). Here, we predict new conjugates of neomycin with two arginine peptide chains binding at specific sites on neomycin [poly-arginine-neomycin-poly-arginine (PA-Neo-PA)]. The rationale for the design of such compounds is to separate two short arginine peptides with neomycin, which may extend the binding region of the CXC chemokine receptor type 4 (CXCR4). We used homology models of CXCR4 and unliganded envelope glycoprotein 120 (HIV-1IIIB gp120) and docked PA-Neo-PAs and APACs to these using a multistep docking procedure. The results indicate that PA-Neo-PAs spread over two negatively charged patches of CXCR4. PA-Neo-PA–CXCR4 complexes are energetically more favorable than AACs/APAC–CXCR4 complexes. Notably, our CXCR4 model and docking procedure can be applied to predict new compounds that are either inhibitors of gp120–CXCR4 binding without affecting stromal cell-derived factor 1α (SDF-1α) chemotaxis activity, or inhibitors of SDF-1α–CXCR4 binding resulting in an anti-metastasis effect. We also predict that PA-Neo-PAs and APACs can interfere with CD4–gp120 binding in unliganded conformation. Figure The r5-Neo-r5-CXCR4 complex. CXCR4 is shown in CPK representation. The negatively charged residues are shown in red and positively charged residues in blue. The r5-Neo-r5 is shown in stick representation, neomycin core is colored yellow and arginine moieties are colored magenta. Two negatively charged patches separated by neutral and positively charged residues are visible.</div>
</front>
</TEI>
<istex><corpusName>springer-journals</corpusName>
<author><json:item><name>Alexander Berchanski</name>
<affiliations><json:string>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</json:string>
</affiliations>
</json:item>
<json:item><name>Aviva Lapidot</name>
<affiliations><json:string>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</json:string>
<json:string>E-mail: aviva.lapidot@weizmann.ac.il</json:string>
</affiliations>
</json:item>
</author>
<subject><json:item><lang><json:string>eng</json:string>
</lang>
<value>CXCR4/SDF-1α</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>gp120/CD4</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>HIV-1 entry inhibitors</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>Molecular modeling and docking</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>Poly-arginine aminoglycoside conjugates</value>
</json:item>
<json:item><lang><json:string>eng</json:string>
</lang>
<value>Predicted compounds</value>
</json:item>
</subject>
<articleId><json:string>401</json:string>
<json:string>s00894-008-0401-1</json:string>
</articleId>
<arkIstex>ark:/67375/VQC-WBV9ZP52-H</arkIstex>
<language><json:string>eng</json:string>
</language>
<originalGenre><json:string>OriginalPaper</json:string>
</originalGenre>
<abstract>Abstract: Aminoglycoside–arginine conjugates (AAC and APAC) are multi-target inhibitors of human immunodeficiency virus type-1 (HIV-1). Here, we predict new conjugates of neomycin with two arginine peptide chains binding at specific sites on neomycin [poly-arginine-neomycin-poly-arginine (PA-Neo-PA)]. The rationale for the design of such compounds is to separate two short arginine peptides with neomycin, which may extend the binding region of the CXC chemokine receptor type 4 (CXCR4). We used homology models of CXCR4 and unliganded envelope glycoprotein 120 (HIV-1IIIB gp120) and docked PA-Neo-PAs and APACs to these using a multistep docking procedure. The results indicate that PA-Neo-PAs spread over two negatively charged patches of CXCR4. PA-Neo-PA–CXCR4 complexes are energetically more favorable than AACs/APAC–CXCR4 complexes. Notably, our CXCR4 model and docking procedure can be applied to predict new compounds that are either inhibitors of gp120–CXCR4 binding without affecting stromal cell-derived factor 1α (SDF-1α) chemotaxis activity, or inhibitors of SDF-1α–CXCR4 binding resulting in an anti-metastasis effect. We also predict that PA-Neo-PAs and APACs can interfere with CD4–gp120 binding in unliganded conformation. Figure The r5-Neo-r5-CXCR4 complex. CXCR4 is shown in CPK representation. The negatively charged residues are shown in red and positively charged residues in blue. The r5-Neo-r5 is shown in stick representation, neomycin core is colored yellow and arginine moieties are colored magenta. Two negatively charged patches separated by neutral and positively charged residues are visible.</abstract>
<qualityIndicators><refBibsNative>false</refBibsNative>
<abstractWordCount>223</abstractWordCount>
<abstractCharCount>1625</abstractCharCount>
<keywordCount>6</keywordCount>
<score>9.676</score>
<pdfWordCount>7305</pdfWordCount>
<pdfCharCount>50336</pdfCharCount>
<pdfVersion>1.3</pdfVersion>
<pdfPageCount>14</pdfPageCount>
<pdfPageSize>595.276 x 790.866 pts</pdfPageSize>
</qualityIndicators>
<title>Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites</title>
<genre><json:string>research-article</json:string>
</genre>
<host><title>Journal of Molecular Modeling</title>
<language><json:string>unknown</json:string>
</language>
<publicationDate>2009</publicationDate>
<copyrightDate>2009</copyrightDate>
<issn><json:string>1610-2940</json:string>
</issn>
<eissn><json:string>0948-5023</json:string>
</eissn>
<journalId><json:string>894</json:string>
</journalId>
<volume>15</volume>
<issue>3</issue>
<pages><first>281</first>
<last>294</last>
</pages>
<genre><json:string>journal</json:string>
</genre>
<subject><json:item><value>Computer Appl. in Life Sciences</value>
</json:item>
<json:item><value>Life Sciences, general</value>
</json:item>
<json:item><value>Health Informatics</value>
</json:item>
<json:item><value>Molecular Medicine</value>
</json:item>
<json:item><value>Biomedicine general</value>
</json:item>
<json:item><value>Computer Applications in Chemistry</value>
</json:item>
</subject>
</host>
<ark><json:string>ark:/67375/VQC-WBV9ZP52-H</json:string>
</ark>
<publicationDate>2009</publicationDate>
<copyrightDate>2008</copyrightDate>
<doi><json:string>10.1007/s00894-008-0401-1</json:string>
</doi>
<id>627E62E8DDCCBDD702E903064164A0C8357E4C4D</id>
<score>1</score>
<fulltext><json:item><extension>pdf</extension>
<original>true</original>
<mimetype>application/pdf</mimetype>
<uri>https://api.istex.fr/ark:/67375/VQC-WBV9ZP52-H/fulltext.pdf</uri>
</json:item>
<json:item><extension>zip</extension>
<original>false</original>
<mimetype>application/zip</mimetype>
<uri>https://api.istex.fr/ark:/67375/VQC-WBV9ZP52-H/bundle.zip</uri>
</json:item>
<istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/VQC-WBV9ZP52-H/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites</title>
</titleStmt>
<publicationStmt><authority>ISTEX</authority>
<publisher scheme="https://scientific-publisher.data.istex.fr">Springer-Verlag</publisher>
<pubPlace>Berlin/Heidelberg</pubPlace>
<availability><licence><p>Springer-Verlag, 2008</p>
</licence>
<p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</p>
</availability>
<date>2008-07-28</date>
</publicationStmt>
<notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note>
<note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note>
<note>Original Paper</note>
</notesStmt>
<sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites</title>
<author xml:id="author-0000"><persName><forename type="first">Alexander</forename>
<surname>Berchanski</surname>
</persName>
<affiliation>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</affiliation>
</author>
<author xml:id="author-0001" corresp="yes"><persName><forename type="first">Aviva</forename>
<surname>Lapidot</surname>
</persName>
<email>aviva.lapidot@weizmann.ac.il</email>
<affiliation>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</affiliation>
</author>
<idno type="istex">627E62E8DDCCBDD702E903064164A0C8357E4C4D</idno>
<idno type="ark">ark:/67375/VQC-WBV9ZP52-H</idno>
<idno type="DOI">10.1007/s00894-008-0401-1</idno>
<idno type="article-id">401</idno>
<idno type="article-id">s00894-008-0401-1</idno>
</analytic>
<monogr><title level="j">Journal of Molecular Modeling</title>
<title level="j" type="sub">Computational Chemistry - Life Sciences - Advanced Materials - New Methods</title>
<title level="j" type="abbrev">J Mol Model</title>
<idno type="pISSN">1610-2940</idno>
<idno type="eISSN">0948-5023</idno>
<idno type="journal-ID">true</idno>
<idno type="issue-article-count">10</idno>
<idno type="volume-issue-count">12</idno>
<imprint><publisher>Springer-Verlag</publisher>
<pubPlace>Berlin/Heidelberg</pubPlace>
<date type="published" when="2009-03-01"></date>
<biblScope unit="volume">15</biblScope>
<biblScope unit="issue">3</biblScope>
<biblScope unit="page" from="281">281</biblScope>
<biblScope unit="page" to="294">294</biblScope>
</imprint>
</monogr>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><creation><date>2008-07-28</date>
</creation>
<langUsage><language ident="en">en</language>
</langUsage>
<abstract xml:lang="en"><p>Abstract: Aminoglycoside–arginine conjugates (AAC and APAC) are multi-target inhibitors of human immunodeficiency virus type-1 (HIV-1). Here, we predict new conjugates of neomycin with two arginine peptide chains binding at specific sites on neomycin [poly-arginine-neomycin-poly-arginine (PA-Neo-PA)]. The rationale for the design of such compounds is to separate two short arginine peptides with neomycin, which may extend the binding region of the CXC chemokine receptor type 4 (CXCR4). We used homology models of CXCR4 and unliganded envelope glycoprotein 120 (HIV-1IIIB gp120) and docked PA-Neo-PAs and APACs to these using a multistep docking procedure. The results indicate that PA-Neo-PAs spread over two negatively charged patches of CXCR4. PA-Neo-PA–CXCR4 complexes are energetically more favorable than AACs/APAC–CXCR4 complexes. Notably, our CXCR4 model and docking procedure can be applied to predict new compounds that are either inhibitors of gp120–CXCR4 binding without affecting stromal cell-derived factor 1α (SDF-1α) chemotaxis activity, or inhibitors of SDF-1α–CXCR4 binding resulting in an anti-metastasis effect. We also predict that PA-Neo-PAs and APACs can interfere with CD4–gp120 binding in unliganded conformation. Figure The r5-Neo-r5-CXCR4 complex. CXCR4 is shown in CPK representation. The negatively charged residues are shown in red and positively charged residues in blue. The r5-Neo-r5 is shown in stick representation, neomycin core is colored yellow and arginine moieties are colored magenta. Two negatively charged patches separated by neutral and positively charged residues are visible.</p>
</abstract>
<textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head>
<item><term>CXCR4/SDF-1α</term>
</item>
<item><term>gp120/CD4</term>
</item>
<item><term>HIV-1 entry inhibitors</term>
</item>
<item><term>Molecular modeling and docking</term>
</item>
<item><term>Poly-arginine aminoglycoside conjugates</term>
</item>
<item><term>Predicted compounds</term>
</item>
</list>
</keywords>
</textClass>
<textClass><keywords scheme="Journal Subject"><list><head>Chemistry</head>
<item><term>Computer Appl. in Life Sciences</term>
</item>
<item><term>Life Sciences, general</term>
</item>
<item><term>Health Informatics</term>
</item>
<item><term>Molecular Medicine</term>
</item>
<item><term>Biomedicine general</term>
</item>
<item><term>Computer Applications in Chemistry</term>
</item>
</list>
</keywords>
</textClass>
</profileDesc>
<revisionDesc><change when="2008-07-28">Created</change>
<change when="2009-03-01">Published</change>
</revisionDesc>
</teiHeader>
</istex:fulltextTEI>
<json:item><extension>txt</extension>
<original>false</original>
<mimetype>text/plain</mimetype>
<uri>https://api.istex.fr/ark:/67375/VQC-WBV9ZP52-H/fulltext.txt</uri>
</json:item>
</fulltext>
<metadata><istex:metadataXml wicri:clean="corpus springer-journals not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration>
<istex:docType PUBLIC="-//Springer-Verlag//DTD A++ V2.4//EN" URI="http://devel.springer.de/A++/V2.4/DTD/A++V2.4.dtd" name="istex:docType"></istex:docType>
<istex:document><Publisher><PublisherInfo><PublisherName>Springer-Verlag</PublisherName>
<PublisherLocation>Berlin/Heidelberg</PublisherLocation>
</PublisherInfo>
<Journal OutputMedium="All"><JournalInfo JournalProductType="ArchiveJournal" NumberingStyle="Unnumbered"><JournalID>894</JournalID>
<JournalPrintISSN>1610-2940</JournalPrintISSN>
<JournalElectronicISSN>0948-5023</JournalElectronicISSN>
<JournalTitle>Journal of Molecular Modeling</JournalTitle>
<JournalSubTitle>Computational Chemistry - Life Sciences - Advanced Materials - New Methods</JournalSubTitle>
<JournalAbbreviatedTitle>J Mol Model</JournalAbbreviatedTitle>
<JournalSubjectGroup><JournalSubject Type="Primary">Chemistry</JournalSubject>
<JournalSubject Type="Secondary">Computer Appl. in Life Sciences </JournalSubject>
<JournalSubject Type="Secondary">Life Sciences, general </JournalSubject>
<JournalSubject Type="Secondary">Health Informatics</JournalSubject>
<JournalSubject Type="Secondary">Molecular Medicine </JournalSubject>
<JournalSubject Type="Secondary">Biomedicine general</JournalSubject>
<JournalSubject Type="Secondary">Computer Applications in Chemistry </JournalSubject>
</JournalSubjectGroup>
</JournalInfo>
<Volume OutputMedium="All"><VolumeInfo TocLevels="0" VolumeType="Regular"><VolumeIDStart>15</VolumeIDStart>
<VolumeIDEnd>15</VolumeIDEnd>
<VolumeIssueCount>12</VolumeIssueCount>
</VolumeInfo>
<Issue IssueType="Regular" OutputMedium="All"><IssueInfo IssueType="Regular" TocLevels="0"><IssueIDStart>3</IssueIDStart>
<IssueIDEnd>3</IssueIDEnd>
<IssueArticleCount>10</IssueArticleCount>
<IssueHistory><OnlineDate><Year>2009</Year>
<Month>1</Month>
<Day>20</Day>
</OnlineDate>
<PrintDate><Year>2009</Year>
<Month>1</Month>
<Day>19</Day>
</PrintDate>
<CoverDate><Year>2009</Year>
<Month>3</Month>
</CoverDate>
<PricelistYear>2009</PricelistYear>
</IssueHistory>
<IssueCopyright><CopyrightHolderName>Springer-Verlag</CopyrightHolderName>
<CopyrightYear>2009</CopyrightYear>
</IssueCopyright>
</IssueInfo>
<Article ID="s00894-008-0401-1" OutputMedium="All"><ArticleInfo ArticleType="OriginalPaper" ContainsESM="No" Language="En" NumberingStyle="Unnumbered" TocLevels="0"><ArticleID>401</ArticleID>
<ArticleDOI>10.1007/s00894-008-0401-1</ArticleDOI>
<ArticleCitationID>281</ArticleCitationID>
<ArticleSequenceNumber>6</ArticleSequenceNumber>
<ArticleTitle Language="En">Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites</ArticleTitle>
<ArticleCategory>Original Paper</ArticleCategory>
<ArticleFirstPage>281</ArticleFirstPage>
<ArticleLastPage>294</ArticleLastPage>
<ArticleHistory><RegistrationDate><Year>2008</Year>
<Month>11</Month>
<Day>6</Day>
</RegistrationDate>
<Received><Year>2008</Year>
<Month>7</Month>
<Day>28</Day>
</Received>
<Accepted><Year>2008</Year>
<Month>10</Month>
<Day>3</Day>
</Accepted>
<OnlineDate><Year>2008</Year>
<Month>12</Month>
<Day>5</Day>
</OnlineDate>
</ArticleHistory>
<ArticleCopyright><CopyrightHolderName>Springer-Verlag</CopyrightHolderName>
<CopyrightYear>2008</CopyrightYear>
</ArticleCopyright>
<ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant>
<AbstractGrant Grant="OpenAccess"></AbstractGrant>
<BodyPDFGrant Grant="Restricted"></BodyPDFGrant>
<BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant>
<BibliographyGrant Grant="Restricted"></BibliographyGrant>
<ESMGrant Grant="Restricted"></ESMGrant>
</ArticleGrants>
</ArticleInfo>
<ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Alexander</GivenName>
<FamilyName>Berchanski</FamilyName>
</AuthorName>
</Author>
<Author AffiliationIDS="Aff1" CorrespondingAffiliationID="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Aviva</GivenName>
<FamilyName>Lapidot</FamilyName>
</AuthorName>
<Contact><Phone>+972-8-9343413</Phone>
<Fax>+972-8-9344142</Fax>
<Email>aviva.lapidot@weizmann.ac.il</Email>
</Contact>
</Author>
<Affiliation ID="Aff1"><OrgDivision>Department of Organic Chemistry</OrgDivision>
<OrgName>The Weizmann Institute of Science</OrgName>
<OrgAddress><City>Rehovot</City>
<Postcode>76100</Postcode>
<Country Code="IL">Israel</Country>
</OrgAddress>
</Affiliation>
</AuthorGroup>
<Abstract ID="Abs1" Language="En"><Heading>Abstract</Heading>
<Para TextBreak="No">Aminoglycoside–arginine conjugates (AAC and APAC) are multi-target inhibitors of human immunodeficiency virus type-1 (HIV-1). Here, we predict new conjugates of neomycin with two arginine peptide chains binding at specific sites on neomycin [poly-arginine-neomycin-poly-arginine (PA-Neo-PA)]. The rationale for the design of such compounds is to separate two short arginine peptides with neomycin, which may extend the binding region of the CXC chemokine receptor type 4 (CXCR4). We used homology models of CXCR4 and unliganded envelope glycoprotein 120 (HIV-1<Subscript>IIIB</Subscript>
gp120) and docked PA-Neo-PAs and APACs to these using a multistep docking procedure. The results indicate that PA-Neo-PAs spread over two negatively charged patches of CXCR4. PA-Neo-PA–CXCR4 complexes are energetically more favorable than AACs/APAC–CXCR4 complexes. Notably, our CXCR4 model and docking procedure can be applied to predict new compounds that are either inhibitors of gp120–CXCR4 binding without affecting stromal cell-derived factor 1α (SDF-1α) chemotaxis activity, or inhibitors of SDF-1α–CXCR4 binding resulting in an anti-metastasis effect. We also predict that PA-Neo-PAs and APACs can interfere with CD4–gp120 binding in unliganded conformation.</Para>
<Para OutputMedium="Online" TextBreak="No"><Figure Category="Standard" Float="No" ID="Figa"><Caption Language="En"><CaptionNumber>Figure</CaptionNumber>
<CaptionContent><SimplePara OutputMedium="Online">The r5-Neo-r5-CXCR4 complex. CXCR4 is shown in CPK representation. The negatively charged residues are shown in <Emphasis Type="Italic">red</Emphasis>
and positively charged residues in <Emphasis Type="Italic">blue</Emphasis>
. The r5-Neo-r5 is shown in stick representation, neomycin core is colored <Emphasis Type="Italic">yellow</Emphasis>
and arginine moieties are colored <Emphasis Type="Italic">magenta</Emphasis>
. Two negatively charged patches separated by neutral and positively charged residues are visible.</SimplePara>
</CaptionContent>
</Caption>
<MediaObject ID="MO2"><ImageObject Color="Color" FileRef="MediaObjects/894_2008_401_Figa_HTML.gif" Format="GIF" Rendition="HTML" Type="LinedrawHalftone"></ImageObject>
</MediaObject>
</Figure>
</Para>
</Abstract>
<KeywordGroup Language="En"><Heading>Keywords</Heading>
<Keyword>CXCR4/SDF-1α</Keyword>
<Keyword>gp120/CD4</Keyword>
<Keyword>HIV-1 entry inhibitors</Keyword>
<Keyword>Molecular modeling and docking</Keyword>
<Keyword>Poly-arginine aminoglycoside conjugates</Keyword>
<Keyword>Predicted compounds</Keyword>
</KeywordGroup>
</ArticleHeader>
<NoBody></NoBody>
</Article>
</Issue>
</Volume>
</Journal>
</Publisher>
</istex:document>
</istex:metadataXml>
<mods version="3.6"><titleInfo lang="en"><title>Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites</title>
</titleInfo>
<titleInfo type="alternative" contentType="CDATA"><title>Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites</title>
</titleInfo>
<name type="personal"><namePart type="given">Alexander</namePart>
<namePart type="family">Berchanski</namePart>
<affiliation>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal" displayLabel="corresp"><namePart type="given">Aviva</namePart>
<namePart type="family">Lapidot</namePart>
<affiliation>Department of Organic Chemistry, The Weizmann Institute of Science, 76100, Rehovot, Israel</affiliation>
<affiliation>E-mail: aviva.lapidot@weizmann.ac.il</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<typeOfResource>text</typeOfResource>
<genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre>
<originInfo><publisher>Springer-Verlag</publisher>
<place><placeTerm type="text">Berlin/Heidelberg</placeTerm>
</place>
<dateCreated encoding="w3cdtf">2008-07-28</dateCreated>
<dateIssued encoding="w3cdtf">2009-03-01</dateIssued>
<copyrightDate encoding="w3cdtf">2008</copyrightDate>
</originInfo>
<language><languageTerm type="code" authority="rfc3066">en</languageTerm>
<languageTerm type="code" authority="iso639-2b">eng</languageTerm>
</language>
<abstract lang="en">Abstract: Aminoglycoside–arginine conjugates (AAC and APAC) are multi-target inhibitors of human immunodeficiency virus type-1 (HIV-1). Here, we predict new conjugates of neomycin with two arginine peptide chains binding at specific sites on neomycin [poly-arginine-neomycin-poly-arginine (PA-Neo-PA)]. The rationale for the design of such compounds is to separate two short arginine peptides with neomycin, which may extend the binding region of the CXC chemokine receptor type 4 (CXCR4). We used homology models of CXCR4 and unliganded envelope glycoprotein 120 (HIV-1IIIB gp120) and docked PA-Neo-PAs and APACs to these using a multistep docking procedure. The results indicate that PA-Neo-PAs spread over two negatively charged patches of CXCR4. PA-Neo-PA–CXCR4 complexes are energetically more favorable than AACs/APAC–CXCR4 complexes. Notably, our CXCR4 model and docking procedure can be applied to predict new compounds that are either inhibitors of gp120–CXCR4 binding without affecting stromal cell-derived factor 1α (SDF-1α) chemotaxis activity, or inhibitors of SDF-1α–CXCR4 binding resulting in an anti-metastasis effect. We also predict that PA-Neo-PAs and APACs can interfere with CD4–gp120 binding in unliganded conformation. Figure The r5-Neo-r5-CXCR4 complex. CXCR4 is shown in CPK representation. The negatively charged residues are shown in red and positively charged residues in blue. The r5-Neo-r5 is shown in stick representation, neomycin core is colored yellow and arginine moieties are colored magenta. Two negatively charged patches separated by neutral and positively charged residues are visible.</abstract>
<note>Original Paper</note>
<subject lang="en"><genre>Keywords</genre>
<topic>CXCR4/SDF-1α</topic>
<topic>gp120/CD4</topic>
<topic>HIV-1 entry inhibitors</topic>
<topic>Molecular modeling and docking</topic>
<topic>Poly-arginine aminoglycoside conjugates</topic>
<topic>Predicted compounds</topic>
</subject>
<relatedItem type="host"><titleInfo><title>Journal of Molecular Modeling</title>
<subTitle>Computational Chemistry - Life Sciences - Advanced Materials - New Methods</subTitle>
</titleInfo>
<titleInfo type="abbreviated"><title>J Mol Model</title>
</titleInfo>
<genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre>
<originInfo><publisher>Springer</publisher>
<dateIssued encoding="w3cdtf">2009-01-20</dateIssued>
<copyrightDate encoding="w3cdtf">2009</copyrightDate>
</originInfo>
<subject><genre>Chemistry</genre>
<topic>Computer Appl. in Life Sciences</topic>
<topic>Life Sciences, general</topic>
<topic>Health Informatics</topic>
<topic>Molecular Medicine</topic>
<topic>Biomedicine general</topic>
<topic>Computer Applications in Chemistry</topic>
</subject>
<identifier type="ISSN">1610-2940</identifier>
<identifier type="eISSN">0948-5023</identifier>
<identifier type="JournalID">894</identifier>
<identifier type="IssueArticleCount">10</identifier>
<identifier type="VolumeIssueCount">12</identifier>
<part><date>2009</date>
<detail type="volume"><number>15</number>
<caption>vol.</caption>
</detail>
<detail type="issue"><number>3</number>
<caption>no.</caption>
</detail>
<extent unit="pages"><start>281</start>
<end>294</end>
</extent>
</part>
<recordInfo><recordOrigin>Springer-Verlag, 2009</recordOrigin>
</recordInfo>
</relatedItem>
<identifier type="istex">627E62E8DDCCBDD702E903064164A0C8357E4C4D</identifier>
<identifier type="ark">ark:/67375/VQC-WBV9ZP52-H</identifier>
<identifier type="DOI">10.1007/s00894-008-0401-1</identifier>
<identifier type="ArticleID">401</identifier>
<identifier type="ArticleID">s00894-008-0401-1</identifier>
<accessCondition type="use and reproduction" contentType="copyright">Springer-Verlag, 2008</accessCondition>
<recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource>
<recordOrigin>Springer-Verlag, 2008</recordOrigin>
</recordInfo>
</mods>
<json:item><extension>json</extension>
<original>false</original>
<mimetype>application/json</mimetype>
<uri>https://api.istex.fr/ark:/67375/VQC-WBV9ZP52-H/record.json</uri>
</json:item>
</metadata>
<serie></serie>
</istex>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A39 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 000A39 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= MersV1 |flux= Istex |étape= Corpus |type= RBID |clé= ISTEX:627E62E8DDCCBDD702E903064164A0C8357E4C4D |texte= Computer-based design of novel HIV-1 entry inhibitors: neomycin conjugated to arginine peptides at two specific sites }}
![]() | This area was generated with Dilib version V0.6.33. | ![]() |