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.
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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.
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DOI: 10.1007/s00894-008-0401-1
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<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. 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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. 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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)
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