Mapping of a discontinuous and highly conformational binding site on follicle stimulating hormone subunit-β (FSH-β) using domain Scan™ and Matrix Scan™ technology
Identifieur interne : 000685 ( Istex/Corpus ); précédent : 000684; suivant : 000686Mapping of a discontinuous and highly conformational binding site on follicle stimulating hormone subunit-β (FSH-β) using domain Scan™ and Matrix Scan™ technology
Auteurs : Peter Timmerman ; Evert Van Dijk ; Wouter Puijk ; Wim Schaaper ; Jerry Slootstra ; Stephen J. Carlisle ; John Coley ; Steve Eida ; M. Gani ; Tim Hunt ; Paul Perry ; Gerry Piron ; Rob H. MeloenSource :
- Molecular Diversity [ 1381-1991 ] ; 2004-06-01.
English descriptors
Abstract
Abstract: This paper describes the application of two novel screening technologies, i.e. Domain Scan™ (24- and 30-mer peptides) and Matrix Scan™ (24-mer peptides)technology, in the mapping of a discontinuous epitope on FSH-β for a series of 20 monoclonal antibodies. 11 out of 20 mAb's, mapping of which was not successful by conventional Pepscan™ technology (12-merpeptides), showed selective binding to peptide-constructs corresponding to the β3-loop of FSH in the Domain™ and/or Matrix Scan™. Systematic replacement analysis studies with peptide-construct 57VYETVRVPGCAC-SAc-ADSLYTYPVATQ81 revealed that for most mAb's the amino acids R62, A70,D71, and L73 form the core of the epitope. A DomainScan™ performed in the C-O format showed highly selective binding for mAb's 1 and 2 with only three β1-β3 peptide-constructs covering the residues 60TVRVPGCAHHADSLY74 in combination with 10IAIEKEECRFAI21, while for mAb 10 binding was observed with peptide-constructs containing the C-terminal residues97RGLGPSYCSFGEMKE114 in combination with the residues 10IAIEKEECRFAI21. A Matrix Scan™ of mAb 17 showed that peptides from four different regions on FSH (1st strand β3-loop, α1-loop, longα2-loop, det. loop) showed enhanced binding in combination with several 70ADSL73-containing peptides. BIACORE measurements with mAb's 1, 2, 13, and 17 using a set of 21 different peptide(-construct)s partially confirmed the Domain and MatrixScan™ screening results. Only 24- and 33-mer peptides covering both the 1st and 2nd strand of the β3-loop showed measurable binding. Cyclic β3-loop peptide mimics were found to bind significantly stronger (Kd∼ 5 μM) than the lineair analogues, in agreement with the fact that the discontinuous epitope is part of a loop structure. Coupling of the lineair β1-peptide 10IAIEKEECRFAI21to the linear β3-peptide*52TFKELVYETVRVPGCAHHADSLYTYPVATQAH83# via disulfide bond formation showed a 2–3 fold increase in Kd, thus conforming participation of the β 1-loop in antibody binding for these mAb's.
Url:
DOI: 10.1023/B:MODI.0000025650.94399.bb
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Carlisle</name><affiliation><mods:affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Coley, John" sort="Coley, John" uniqKey="Coley J" first="John" last="Coley">John Coley</name><affiliation><mods:affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Eida, Steve" sort="Eida, Steve" uniqKey="Eida S" first="Steve" last="Eida">Steve Eida</name><affiliation><mods:affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Gani, M" sort="Gani, M" uniqKey="Gani M" first="M." last="Gani">M. Gani</name><affiliation><mods:affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Hunt, Tim" sort="Hunt, Tim" uniqKey="Hunt T" first="Tim" last="Hunt">Tim Hunt</name><affiliation><mods:affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Perry, Paul" sort="Perry, Paul" uniqKey="Perry P" first="Paul" last="Perry">Paul Perry</name><affiliation><mods:affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Piron, Gerry" sort="Piron, Gerry" uniqKey="Piron G" first="Gerry" last="Piron">Gerry Piron</name><affiliation><mods:affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</mods:affiliation></affiliation></author><author><name sortKey="Meloen, Rob H" sort="Meloen, Rob H" uniqKey="Meloen R" first="Rob H." last="Meloen">Rob H. Meloen</name><affiliation><mods:affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</mods:affiliation></affiliation><affiliation><mods:affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Molecular Diversity</title><title level="j" type="abbrev">Mol Divers</title><idno type="ISSN">1381-1991</idno><idno type="eISSN">1573-501X</idno><imprint><publisher>Kluwer Academic Publishers</publisher><pubPlace>Dordrecht</pubPlace><date type="published" when="2004-06-01">2004-06-01</date><biblScope unit="volume">8</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="61">61</biblScope><biblScope unit="page" to="77">77</biblScope></imprint><idno type="ISSN">1381-1991</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1381-1991</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>affinity measurements</term><term>epitope mapping</term><term>fertility hormones</term><term>peptides</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: This paper describes the application of two novel screening technologies, i.e. Domain Scan™ (24- and 30-mer peptides) and Matrix Scan™ (24-mer peptides)technology, in the mapping of a discontinuous epitope on FSH-β for a series of 20 monoclonal antibodies. 11 out of 20 mAb's, mapping of which was not successful by conventional Pepscan™ technology (12-merpeptides), showed selective binding to peptide-constructs corresponding to the β3-loop of FSH in the Domain™ and/or Matrix Scan™. Systematic replacement analysis studies with peptide-construct 57VYETVRVPGCAC-SAc-ADSLYTYPVATQ81 revealed that for most mAb's the amino acids R62, A70,D71, and L73 form the core of the epitope. A DomainScan™ performed in the C-O format showed highly selective binding for mAb's 1 and 2 with only three β1-β3 peptide-constructs covering the residues 60TVRVPGCAHHADSLY74 in combination with 10IAIEKEECRFAI21, while for mAb 10 binding was observed with peptide-constructs containing the C-terminal residues97RGLGPSYCSFGEMKE114 in combination with the residues 10IAIEKEECRFAI21. A Matrix Scan™ of mAb 17 showed that peptides from four different regions on FSH (1st strand β3-loop, α1-loop, longα2-loop, det. loop) showed enhanced binding in combination with several 70ADSL73-containing peptides. BIACORE measurements with mAb's 1, 2, 13, and 17 using a set of 21 different peptide(-construct)s partially confirmed the Domain and MatrixScan™ screening results. Only 24- and 33-mer peptides covering both the 1st and 2nd strand of the β3-loop showed measurable binding. Cyclic β3-loop peptide mimics were found to bind significantly stronger (Kd∼ 5 μM) than the lineair analogues, in agreement with the fact that the discontinuous epitope is part of a loop structure. Coupling of the lineair β1-peptide 10IAIEKEECRFAI21to the linear β3-peptide*52TFKELVYETVRVPGCAHHADSLYTYPVATQAH83# via disulfide bond formation showed a 2–3 fold increase in Kd, thus conforming participation of the β 1-loop in antibody binding for these mAb's.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Peter Timmerman</name><affiliations><json:string>Pepscan Systems B.V., Lelystad, The Netherlands</json:string><json:string>E-mail: p.timmerman@pepscan.nl</json:string></affiliations></json:item><json:item><name>Evert Van Dijk</name><affiliations><json:string>Pepscan Systems B.V., Lelystad, The Netherlands</json:string></affiliations></json:item><json:item><name>Wouter Puijk</name><affiliations><json:string>Pepscan Systems B.V., Lelystad, The Netherlands</json:string></affiliations></json:item><json:item><name>Wim Schaaper</name><affiliations><json:string>Pepscan Systems B.V., Lelystad, The Netherlands</json:string></affiliations></json:item><json:item><name>Jerry Slootstra</name><affiliations><json:string>Pepscan Systems B.V., Lelystad, The Netherlands</json:string></affiliations></json:item><json:item><name>Stephen J. Carlisle</name><affiliations><json:string>Unipath Limited, Priory Business Park, Bedford, United Kingdom</json:string></affiliations></json:item><json:item><name>John Coley</name><affiliations><json:string>Unipath Limited, Priory Business Park, Bedford, United Kingdom</json:string></affiliations></json:item><json:item><name>Steve Eida</name><affiliations><json:string>Unipath Limited, Priory Business Park, Bedford, United Kingdom</json:string></affiliations></json:item><json:item><name>M. Gani</name><affiliations><json:string>Unipath Limited, Priory Business Park, Bedford, United Kingdom</json:string></affiliations></json:item><json:item><name>Tim Hunt</name><affiliations><json:string>Unipath Limited, Priory Business Park, Bedford, United Kingdom</json:string></affiliations></json:item><json:item><name>Paul Perry</name><affiliations><json:string>Unipath Limited, Priory Business Park, Bedford, United Kingdom</json:string></affiliations></json:item><json:item><name>Gerry Piron</name><affiliations><json:string>Unipath Limited, Priory Business Park, Bedford, United Kingdom</json:string></affiliations></json:item><json:item><name>Rob H. Meloen</name><affiliations><json:string>Pepscan Systems B.V., Lelystad, The Netherlands</json:string><json:string>Unipath Limited, Priory Business Park, Bedford, United Kingdom</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>affinity measurements</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>epitope mapping</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>fertility hormones</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>peptides</value></json:item></subject><articleId><json:string>5266955</json:string><json:string>Art2</json:string></articleId><arkIstex>ark:/67375/VQC-KQRHF3Z9-6</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: This paper describes the application of two novel screening technologies, i.e. Domain Scan™ (24- and 30-mer peptides) and Matrix Scan™ (24-mer peptides)technology, in the mapping of a discontinuous epitope on FSH-β for a series of 20 monoclonal antibodies. 11 out of 20 mAb's, mapping of which was not successful by conventional Pepscan™ technology (12-merpeptides), showed selective binding to peptide-constructs corresponding to the β3-loop of FSH in the Domain™ and/or Matrix Scan™. Systematic replacement analysis studies with peptide-construct 57VYETVRVPGCAC-SAc-ADSLYTYPVATQ81 revealed that for most mAb's the amino acids R62, A70,D71, and L73 form the core of the epitope. A DomainScan™ performed in the C-O format showed highly selective binding for mAb's 1 and 2 with only three β1-β3 peptide-constructs covering the residues 60TVRVPGCAHHADSLY74 in combination with 10IAIEKEECRFAI21, while for mAb 10 binding was observed with peptide-constructs containing the C-terminal residues97RGLGPSYCSFGEMKE114 in combination with the residues 10IAIEKEECRFAI21. A Matrix Scan™ of mAb 17 showed that peptides from four different regions on FSH (1st strand β3-loop, α1-loop, longα2-loop, det. loop) showed enhanced binding in combination with several 70ADSL73-containing peptides. BIACORE measurements with mAb's 1, 2, 13, and 17 using a set of 21 different peptide(-construct)s partially confirmed the Domain and MatrixScan™ screening results. Only 24- and 33-mer peptides covering both the 1st and 2nd strand of the β3-loop showed measurable binding. Cyclic β3-loop peptide mimics were found to bind significantly stronger (Kd∼ 5 μM) than the lineair analogues, in agreement with the fact that the discontinuous epitope is part of a loop structure. Coupling of the lineair β1-peptide 10IAIEKEECRFAI21to the linear β3-peptide*52TFKELVYETVRVPGCAHHADSLYTYPVATQAH83# via disulfide bond formation showed a 2–3 fold increase in Kd, thus conforming participation of the β 1-loop in antibody binding for these mAb's.</abstract><qualityIndicators><score>10</score><pdfWordCount>8759</pdfWordCount><pdfCharCount>52226</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>17</pdfPageCount><pdfPageSize>595 x 842 pts (A4)</pdfPageSize><refBibsNative>false</refBibsNative><abstractWordCount>283</abstractWordCount><abstractCharCount>2017</abstractCharCount><keywordCount>4</keywordCount></qualityIndicators><title>Mapping of a discontinuous and highly conformational binding site on follicle stimulating hormone subunit-β (FSH-β) using domain Scan™ and Matrix Scan™ technology</title><genre><json:string>research-article</json:string></genre><host><title>Molecular Diversity</title><language><json:string>unknown</json:string></language><publicationDate>2004</publicationDate><copyrightDate>2004</copyrightDate><issn><json:string>1381-1991</json:string></issn><eissn><json:string>1573-501X</json:string></eissn><journalId><json:string>11030</json:string></journalId><volume>8</volume><issue>2</issue><pages><first>61</first><last>77</last></pages><genre><json:string>journal</json:string></genre><editor><json:item><name>Rob H. Meloen</name></json:item></editor><subject><json:item><value>Analytical Chemistry</value></json:item><json:item><value>Organic Chemistry</value></json:item><json:item><value>Polymer Sciences</value></json:item><json:item><value>Pharmacy</value></json:item></subject></host><ark><json:string>ark:/67375/VQC-KQRHF3Z9-6</json:string></ark><publicationDate>2004</publicationDate><copyrightDate>2004</copyrightDate><doi><json:string>10.1023/B:MODI.0000025650.94399.bb</json:string></doi><id>CDFAACC91736BF8468E37BDB8FA45EB2D00F466B</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-KQRHF3Z9-6/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-KQRHF3Z9-6/bundle.zip</uri></json:item><istex:fulltextTEI 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type="inbook"><analytic><title level="a" type="main" xml:lang="en">Mapping of a discontinuous and highly conformational binding site on follicle stimulating hormone subunit-β (FSH-β) using domain Scan™ and Matrix Scan™ technology</title><author xml:id="author-0000" corresp="yes"><persName><forename type="first">Peter</forename><surname>Timmerman</surname></persName><email>p.timmerman@pepscan.nl</email><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Evert</forename><surname>Van Dijk</surname></persName><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Wouter</forename><surname>Puijk</surname></persName><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Wim</forename><surname>Schaaper</surname></persName><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Jerry</forename><surname>Slootstra</surname></persName><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Stephen</forename><surname>Carlisle</surname></persName><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation></author><author xml:id="author-0006"><persName><forename type="first">John</forename><surname>Coley</surname></persName><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Steve</forename><surname>Eida</surname></persName><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation></author><author xml:id="author-0008"><persName><forename type="first">M.</forename><surname>Gani</surname></persName><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation></author><author xml:id="author-0009"><persName><forename type="first">Tim</forename><surname>Hunt</surname></persName><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation></author><author xml:id="author-0010"><persName><forename type="first">Paul</forename><surname>Perry</surname></persName><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation></author><author xml:id="author-0011"><persName><forename type="first">Gerry</forename><surname>Piron</surname></persName><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation></author><author xml:id="author-0012"><persName><forename type="first">Rob</forename><surname>Meloen</surname></persName><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation></author><idno type="istex">CDFAACC91736BF8468E37BDB8FA45EB2D00F466B</idno><idno type="ark">ark:/67375/VQC-KQRHF3Z9-6</idno><idno type="DOI">10.1023/B:MODI.0000025650.94399.bb</idno><idno type="article-id">5266955</idno><idno type="article-id">Art2</idno></analytic><monogr><title level="j">Molecular Diversity</title><title level="j" type="abbrev">Mol Divers</title><idno type="pISSN">1381-1991</idno><idno type="eISSN">1573-501X</idno><idno type="journal-ID">true</idno><idno type="issue-article-count">13</idno><idno type="volume-issue-count">4</idno><editor xml:id="book-author-0000"><persName><forename type="first">Rob</forename><forename type="first">H.</forename><surname>Meloen</surname></persName></editor><imprint><publisher>Kluwer Academic Publishers</publisher><pubPlace>Dordrecht</pubPlace><date type="published" when="2004-06-01"></date><biblScope unit="volume">8</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="61">61</biblScope><biblScope unit="page" to="77">77</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2004</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: This paper describes the application of two novel screening technologies, i.e. Domain Scan™ (24- and 30-mer peptides) and Matrix Scan™ (24-mer peptides)technology, in the mapping of a discontinuous epitope on FSH-β for a series of 20 monoclonal antibodies. 11 out of 20 mAb's, mapping of which was not successful by conventional Pepscan™ technology (12-merpeptides), showed selective binding to peptide-constructs corresponding to the β3-loop of FSH in the Domain™ and/or Matrix Scan™. Systematic replacement analysis studies with peptide-construct 57VYETVRVPGCAC-SAc-ADSLYTYPVATQ81 revealed that for most mAb's the amino acids R62, A70,D71, and L73 form the core of the epitope. A DomainScan™ performed in the C-O format showed highly selective binding for mAb's 1 and 2 with only three β1-β3 peptide-constructs covering the residues 60TVRVPGCAHHADSLY74 in combination with 10IAIEKEECRFAI21, while for mAb 10 binding was observed with peptide-constructs containing the C-terminal residues97RGLGPSYCSFGEMKE114 in combination with the residues 10IAIEKEECRFAI21. A Matrix Scan™ of mAb 17 showed that peptides from four different regions on FSH (1st strand β3-loop, α1-loop, longα2-loop, det. loop) showed enhanced binding in combination with several 70ADSL73-containing peptides. BIACORE measurements with mAb's 1, 2, 13, and 17 using a set of 21 different peptide(-construct)s partially confirmed the Domain and MatrixScan™ screening results. Only 24- and 33-mer peptides covering both the 1st and 2nd strand of the β3-loop showed measurable binding. Cyclic β3-loop peptide mimics were found to bind significantly stronger (Kd∼ 5 μM) than the lineair analogues, in agreement with the fact that the discontinuous epitope is part of a loop structure. Coupling of the lineair β1-peptide 10IAIEKEECRFAI21to the linear β3-peptide*52TFKELVYETVRVPGCAHHADSLYTYPVATQAH83# via disulfide bond formation showed a 2–3 fold increase in Kd, thus conforming participation of the β 1-loop in antibody binding for these mAb's.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><item><term>affinity measurements</term></item><item><term>epitope mapping</term></item><item><term>fertility hormones</term></item><item><term>peptides</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Chemistry</head><item><term>Analytical Chemistry</term></item><item><term>Organic Chemistry</term></item><item><term>Polymer Sciences</term></item><item><term>Pharmacy</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2004-06-01">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-KQRHF3Z9-6/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>Kluwer Academic Publishers</PublisherName><PublisherLocation>Dordrecht</PublisherLocation></PublisherInfo><Journal><JournalInfo JournalProductType="ArchiveJournal" NumberingStyle="Unnumbered"><JournalID>11030</JournalID><JournalPrintISSN>1381-1991</JournalPrintISSN><JournalElectronicISSN>1573-501X</JournalElectronicISSN><JournalTitle>Molecular Diversity</JournalTitle><JournalAbbreviatedTitle>Mol Divers</JournalAbbreviatedTitle><JournalSubjectGroup><JournalSubject Type="Primary">Chemistry</JournalSubject><JournalSubject Type="Secondary">Analytical Chemistry</JournalSubject><JournalSubject Type="Secondary">Organic Chemistry</JournalSubject><JournalSubject Type="Secondary">Polymer Sciences</JournalSubject><JournalSubject Type="Secondary">Pharmacy</JournalSubject></JournalSubjectGroup></JournalInfo><Volume><VolumeInfo VolumeType="Regular" TocLevels="0"><VolumeIDStart>8</VolumeIDStart><VolumeIDEnd>8</VolumeIDEnd><VolumeIssueCount>4</VolumeIssueCount></VolumeInfo><Issue IssueType="Regular"><IssueInfo TocLevels="0"><IssueIDStart>2</IssueIDStart><IssueIDEnd>2</IssueIDEnd><IssueTitle Language="En">Peptide Libraries and Peptide Drugs</IssueTitle><IssueArticleCount>13</IssueArticleCount><IssueHistory><CoverDate><DateString>2004</DateString><Year>2004</Year><Month>6</Month></CoverDate></IssueHistory><IssueCopyright><CopyrightHolderName>Kluwer Academic Publishers</CopyrightHolderName><CopyrightYear>2004</CopyrightYear></IssueCopyright></IssueInfo><IssueHeader><EditorGroup><Editor><EditorName DisplayOrder="Western"><GivenName>Rob</GivenName><GivenName>H.</GivenName><FamilyName>Meloen</FamilyName></EditorName></Editor></EditorGroup></IssueHeader><Article ID="Art2"><ArticleInfo Language="En" ArticleType="OriginalPaper" NumberingStyle="Unnumbered" TocLevels="0" ContainsESM="No"><ArticleID>5266955</ArticleID><ArticleDOI>10.1023/B:MODI.0000025650.94399.bb</ArticleDOI><ArticleSequenceNumber>2</ArticleSequenceNumber><ArticleTitle Language="En">Mapping of a discontinuous and highly conformational binding site on follicle stimulating hormone subunit-β (FSH-β) using domain Scan™ and Matrix Scan™ technology</ArticleTitle><ArticleFirstPage>61</ArticleFirstPage><ArticleLastPage>77</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2004</Year><Month>10</Month><Day>2</Day></RegistrationDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Kluwer Academic Publishers</CopyrightHolderName><CopyrightYear>2004</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><ArticleContext><JournalID>11030</JournalID><VolumeIDStart>8</VolumeIDStart><VolumeIDEnd>8</VolumeIDEnd><IssueIDStart>2</IssueIDStart><IssueIDEnd>2</IssueIDEnd></ArticleContext></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1" CorrespondingAffiliationID="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Peter</GivenName><FamilyName>Timmerman</FamilyName></AuthorName><Contact><Email>p.timmerman@pepscan.nl</Email></Contact></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Evert</GivenName><FamilyName>Van Dijk</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Wouter</GivenName><FamilyName>Puijk</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Wim</GivenName><FamilyName>Schaaper</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Jerry</GivenName><FamilyName>Slootstra</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Stephen</GivenName><GivenName>J.</GivenName><FamilyName>Carlisle</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>John</GivenName><FamilyName>Coley</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Steve</GivenName><FamilyName>Eida</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>M.</GivenName><FamilyName>Gani</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Tim</GivenName><FamilyName>Hunt</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Paul</GivenName><FamilyName>Perry</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Gerry</GivenName><FamilyName>Piron</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff2"><AuthorName DisplayOrder="Western"><GivenName>Rob</GivenName><GivenName>H.</GivenName><FamilyName>Meloen</FamilyName></AuthorName></Author><Affiliation ID="Aff1"><OrgName>Pepscan Systems B.V.</OrgName><OrgAddress><City>Lelystad</City><Country>The Netherlands</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgName>Unipath Limited</OrgName><OrgAddress><Street>Priory Business Park</Street><City>Bedford</City><Country>United Kingdom</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En"><Heading>Abstract</Heading><Para>This paper describes the application of two novel screening technologies, i.e. Domain Scan™ (24- and 30-mer peptides) and Matrix Scan™ (24-mer peptides)technology, in the mapping of a discontinuous epitope on FSH-β for a series of 20 monoclonal antibodies. 11 out of 20 mAb's, mapping of which was not successful by conventional Pepscan™ technology (12-merpeptides), showed selective binding to peptide-constructs corresponding to the β3-loop of FSH in the Domain™ and/or Matrix Scan™. Systematic replacement analysis studies with peptide-construct <Subscript>57</Subscript>VYETVRVPGCA<Emphasis Type="Bold">C</Emphasis>-<Emphasis Type="Bold">SAc</Emphasis>-ADSLYTYPVATQ<Subscript>81</Subscript> revealed that for most mAb's the amino acids R<Subscript>62</Subscript>, A<Subscript>70</Subscript>,D<Subscript>71</Subscript>, and L<Subscript>73</Subscript> form the core of the epitope. A DomainScan™ performed in the <Emphasis Type="Italic">C-O</Emphasis> format showed highly selective binding for mAb's 1 and 2 with only three β1-β3 peptide-constructs covering the residues <Subscript>60</Subscript>TVRVPGCAHHADSLY<Subscript>74</Subscript> in combination with <Subscript>10</Subscript>IAIEKEECRFAI<Subscript>21</Subscript>, while for mAb 10 binding was observed with peptide-constructs containing the C-terminal residues<Subscript>97</Subscript>RGLGPSYCSFGEMKE<Subscript>114</Subscript> in combination with the residues <Subscript>10</Subscript>IAIEKEECRFAI<Subscript>21</Subscript>. A Matrix Scan™ of mAb 17 showed that peptides from four different regions on FSH (1st strand β3-loop, α1-loop, longα2-loop, det. loop) showed enhanced binding in combination with several <Subscript>70</Subscript>ADSL<Subscript>73</Subscript>-containing peptides. BIACORE measurements with mAb's 1, 2, 13, and 17 using a set of 21 different peptide(-construct)s partially confirmed the Domain and MatrixScan™ screening results. Only 24- and 33-mer peptides covering both the 1st and 2nd strand of the β3-loop showed measurable binding. Cyclic β3-loop peptide mimics were found to bind significantly stronger (K<Subscript>d</Subscript>∼ 5 μM) than the lineair analogues, in agreement with the fact that the discontinuous epitope is part of a loop structure. Coupling of the lineair β1-peptide <Subscript>10</Subscript>IAIEKEECRFAI<Subscript>21</Subscript>to the linear β3-peptide*<Subscript>52</Subscript>TFKELVYETVRVPGCAHHADSLYTYPVATQAH<Subscript>83</Subscript># via disulfide bond formation showed a 2–3 fold increase in K<Subscript>d</Subscript>, thus conforming participation of the β 1-loop in antibody binding for these mAb's.</Para></Abstract><KeywordGroup Language="En"><Keyword>affinity measurements</Keyword><Keyword>epitope mapping</Keyword><Keyword>fertility hormones</Keyword><Keyword>peptides</Keyword></KeywordGroup></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Mapping of a discontinuous and highly conformational binding site on follicle stimulating hormone subunit-β (FSH-β) using domain Scan™ and Matrix Scan™ technology</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Mapping of a discontinuous and highly conformational binding site on follicle stimulating hormone subunit-β (FSH-β) using domain Scan™ and Matrix Scan™ technology</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Peter</namePart><namePart type="family">Timmerman</namePart><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation><affiliation>E-mail: p.timmerman@pepscan.nl</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Evert</namePart><namePart type="family">Van Dijk</namePart><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wouter</namePart><namePart type="family">Puijk</namePart><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wim</namePart><namePart type="family">Schaaper</namePart><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jerry</namePart><namePart type="family">Slootstra</namePart><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stephen</namePart><namePart type="given">J.</namePart><namePart type="family">Carlisle</namePart><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John</namePart><namePart type="family">Coley</namePart><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Steve</namePart><namePart type="family">Eida</namePart><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Gani</namePart><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Tim</namePart><namePart type="family">Hunt</namePart><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul</namePart><namePart type="family">Perry</namePart><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gerry</namePart><namePart type="family">Piron</namePart><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rob</namePart><namePart type="given">H.</namePart><namePart type="family">Meloen</namePart><affiliation>Pepscan Systems B.V., Lelystad, The Netherlands</affiliation><affiliation>Unipath Limited, Priory Business Park, Bedford, United Kingdom</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>Kluwer Academic Publishers</publisher><place><placeTerm type="text">Dordrecht</placeTerm></place><dateIssued encoding="w3cdtf">2004-06-01</dateIssued><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: This paper describes the application of two novel screening technologies, i.e. Domain Scan™ (24- and 30-mer peptides) and Matrix Scan™ (24-mer peptides)technology, in the mapping of a discontinuous epitope on FSH-β for a series of 20 monoclonal antibodies. 11 out of 20 mAb's, mapping of which was not successful by conventional Pepscan™ technology (12-merpeptides), showed selective binding to peptide-constructs corresponding to the β3-loop of FSH in the Domain™ and/or Matrix Scan™. Systematic replacement analysis studies with peptide-construct 57VYETVRVPGCAC-SAc-ADSLYTYPVATQ81 revealed that for most mAb's the amino acids R62, A70,D71, and L73 form the core of the epitope. A DomainScan™ performed in the C-O format showed highly selective binding for mAb's 1 and 2 with only three β1-β3 peptide-constructs covering the residues 60TVRVPGCAHHADSLY74 in combination with 10IAIEKEECRFAI21, while for mAb 10 binding was observed with peptide-constructs containing the C-terminal residues97RGLGPSYCSFGEMKE114 in combination with the residues 10IAIEKEECRFAI21. A Matrix Scan™ of mAb 17 showed that peptides from four different regions on FSH (1st strand β3-loop, α1-loop, longα2-loop, det. loop) showed enhanced binding in combination with several 70ADSL73-containing peptides. BIACORE measurements with mAb's 1, 2, 13, and 17 using a set of 21 different peptide(-construct)s partially confirmed the Domain and MatrixScan™ screening results. Only 24- and 33-mer peptides covering both the 1st and 2nd strand of the β3-loop showed measurable binding. Cyclic β3-loop peptide mimics were found to bind significantly stronger (Kd∼ 5 μM) than the lineair analogues, in agreement with the fact that the discontinuous epitope is part of a loop structure. Coupling of the lineair β1-peptide 10IAIEKEECRFAI21to the linear β3-peptide*52TFKELVYETVRVPGCAHHADSLYTYPVATQAH83# via disulfide bond formation showed a 2–3 fold increase in Kd, thus conforming participation of the β 1-loop in antibody binding for these mAb's.</abstract><subject lang="en"><topic>affinity measurements</topic><topic>epitope mapping</topic><topic>fertility hormones</topic><topic>peptides</topic></subject><relatedItem type="host"><titleInfo><title>Molecular Diversity</title></titleInfo><titleInfo type="abbreviated"><title>Mol Divers</title></titleInfo><name type="personal"><namePart type="given">Rob</namePart><namePart type="given">H.</namePart><namePart type="family">Meloen</namePart><role><roleTerm type="text">editor</roleTerm></role></name><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">2004-06-01</dateIssued><copyrightDate encoding="w3cdtf">2004</copyrightDate></originInfo><subject><genre>Chemistry</genre><topic>Analytical Chemistry</topic><topic>Organic Chemistry</topic><topic>Polymer Sciences</topic><topic>Pharmacy</topic></subject><identifier type="ISSN">1381-1991</identifier><identifier type="eISSN">1573-501X</identifier><identifier type="JournalID">11030</identifier><identifier type="IssueArticleCount">13</identifier><identifier type="VolumeIssueCount">4</identifier><part><date>2004</date><detail type="issue"><title>Peptide Libraries and Peptide Drugs</title></detail><detail type="volume"><number>8</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="pages"><start>61</start><end>77</end></extent></part><recordInfo><recordOrigin>Kluwer Academic Publishers, 2004</recordOrigin></recordInfo></relatedItem><identifier type="istex">CDFAACC91736BF8468E37BDB8FA45EB2D00F466B</identifier><identifier type="ark">ark:/67375/VQC-KQRHF3Z9-6</identifier><identifier type="DOI">10.1023/B:MODI.0000025650.94399.bb</identifier><identifier type="ArticleID">5266955</identifier><identifier type="ArticleID">Art2</identifier><accessCondition type="use and reproduction" contentType="copyright">Kluwer Academic Publishers, 2004</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>Kluwer Academic Publishers, 2004</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-KQRHF3Z9-6/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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