Screening for Galectin-3 Inhibitors from Synthetic Lacto-N-biose Libraries Using Microscale Affinity Chromatography Coupled to Mass Spectrometry
The synthesis and screening of two β-d-Galp-(1-3)-β-d-GlcpN (lacto-N-biose) disaccharide libraries are reported. Solution-phase synthetic modifications at the HO-2‘ and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor m...
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| Veröffentlicht in: | Journal of organic chemistry 2006-09, Vol.71 (19), p.7146-7154 |
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| container_title | Journal of organic chemistry |
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| creator | Fort, Sébastien Kim, Hyo-Sun Hindsgaul, Ole |
| description | The synthesis and screening of two β-d-Galp-(1-3)-β-d-GlcpN (lacto-N-biose) disaccharide libraries are reported. Solution-phase synthetic modifications at the HO-2‘ and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor metastasis, apoptosis, and inflammation. The libraries were screened for galectin-3 binding by microscale frontal affinity chromatography coupled to mass spectrometry (FAC/MS) allowing for rapid ranking of the different inhibitors and the determination of the galectin-3 binding K d's. Compounds bearing a hydrophobic substituent on the NH group showed the highest affinity for the lectin. The N-naphthoyl derivative (K d = 10.6 μM) was the best inhibitor with a 7 times increased affinity as compared to the N-acetyl parent compound (K d = 73.3 μM). |
| doi_str_mv | 10.1021/jo060485v |
| format | Article |
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Solution-phase synthetic modifications at the HO-2‘ and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor metastasis, apoptosis, and inflammation. The libraries were screened for galectin-3 binding by microscale frontal affinity chromatography coupled to mass spectrometry (FAC/MS) allowing for rapid ranking of the different inhibitors and the determination of the galectin-3 binding K d's. Compounds bearing a hydrophobic substituent on the NH group showed the highest affinity for the lectin. 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Nucleosides and nucleotides ; Chemistry ; Chromatography, Affinity ; Condensed benzenic and aromatic compounds ; Disaccharides - chemical synthesis ; Disaccharides - chemistry ; Exact sciences and technology ; Galectin 3 - antagonists & inhibitors ; Ligands ; Mass Spectrometry ; Molecular Structure ; Organic chemistry ; Preparations and properties ; Protein Binding</subject><ispartof>Journal of organic chemistry, 2006-09, Vol.71 (19), p.7146-7154</ispartof><rights>Copyright © 2006 American Chemical Society</rights><rights>2007 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a481t-5c075b5161a4fe8ee14954608525a2f95249e5179283b98d72ae5e695d9804553</citedby><cites>FETCH-LOGICAL-a481t-5c075b5161a4fe8ee14954608525a2f95249e5179283b98d72ae5e695d9804553</cites><orcidid>0000-0002-6133-9900</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jo060485v$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jo060485v$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,315,781,785,886,2766,27080,27928,27929,56742,56792</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18098980$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16958507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00305783$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Fort, Sébastien</creatorcontrib><creatorcontrib>Kim, Hyo-Sun</creatorcontrib><creatorcontrib>Hindsgaul, Ole</creatorcontrib><title>Screening for Galectin-3 Inhibitors from Synthetic Lacto-N-biose Libraries Using Microscale Affinity Chromatography Coupled to Mass Spectrometry</title><title>Journal of organic chemistry</title><addtitle>J. Org. Chem</addtitle><description>The synthesis and screening of two β-d-Galp-(1-3)-β-d-GlcpN (lacto-N-biose) disaccharide libraries are reported. Solution-phase synthetic modifications at the HO-2‘ and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor metastasis, apoptosis, and inflammation. The libraries were screened for galectin-3 binding by microscale frontal affinity chromatography coupled to mass spectrometry (FAC/MS) allowing for rapid ranking of the different inhibitors and the determination of the galectin-3 binding K d's. Compounds bearing a hydrophobic substituent on the NH group showed the highest affinity for the lectin. The N-naphthoyl derivative (K d = 10.6 μM) was the best inhibitor with a 7 times increased affinity as compared to the N-acetyl parent compound (K d = 73.3 μM).</description><subject>Acetylglucosamine - analogs & derivatives</subject><subject>Acetylglucosamine - chemical synthesis</subject><subject>Acetylglucosamine - chemistry</subject><subject>Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides</subject><subject>Carbohydrates. Nucleosides and nucleotides</subject><subject>Chemistry</subject><subject>Chromatography, Affinity</subject><subject>Condensed benzenic and aromatic compounds</subject><subject>Disaccharides - chemical synthesis</subject><subject>Disaccharides - chemistry</subject><subject>Exact sciences and technology</subject><subject>Galectin 3 - antagonists & inhibitors</subject><subject>Ligands</subject><subject>Mass Spectrometry</subject><subject>Molecular Structure</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Protein Binding</subject><issn>0022-3263</issn><issn>1520-6904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkU9v0zAUwCMEYt3gwBdAvoC0Q8CO8xLnWHWwTWQDKd2Fi-WkL4tHGgfbmei34CPjqFV7wRfLzz_93r8oesfoJ0YT9vnJ0IymAp5fRAsGCY2zgqYvowWlSRLzJONn0blzTzQcAHgdnbGsAAE0X0R_q8YiDnp4JK2x5Fr12Hg9xJzcDp2utTfWkdaaLal2g-_Q64aUqvEmvo9rbRySUtdWWY2OPLhZc6cba1wTRGTZtnrQfkdWXTAobx6tGrvwNNPY44Z4Q-6Uc6QaQ9JAoLe7N9GrVvUO3x7ui-jh65f16iYuv1_frpZlrFLBfAwNzaEGljGVtigQWVpAmlEBCaikLSBJCwSWF4ngdSE2eaIQMLS9KQRNAfhFdLn3dqqXo9VbZXfSKC1vlqWcY5RyCrngzyywH_fsaM3vCZ2XW-0a7Hs1oJmczITgnIdMR-k8AmexPZoZlfOq5HFVgX1_kE71Fjcn8rCbAHw4AGoeZ2vV0Gh34gQtRGgmcPGe087jn-O_sr9klvMc5PpHJdf3eXUFV9_kz5NXNS7UM9khzPk_Bf4Dt4W2uw</recordid><startdate>20060915</startdate><enddate>20060915</enddate><creator>Fort, Sébastien</creator><creator>Kim, Hyo-Sun</creator><creator>Hindsgaul, Ole</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-6133-9900</orcidid></search><sort><creationdate>20060915</creationdate><title>Screening for Galectin-3 Inhibitors from Synthetic Lacto-N-biose Libraries Using Microscale Affinity Chromatography Coupled to Mass Spectrometry</title><author>Fort, Sébastien ; Kim, Hyo-Sun ; Hindsgaul, Ole</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a481t-5c075b5161a4fe8ee14954608525a2f95249e5179283b98d72ae5e695d9804553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Acetylglucosamine - analogs & derivatives</topic><topic>Acetylglucosamine - chemical synthesis</topic><topic>Acetylglucosamine - chemistry</topic><topic>Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides</topic><topic>Carbohydrates. Nucleosides and nucleotides</topic><topic>Chemistry</topic><topic>Chromatography, Affinity</topic><topic>Condensed benzenic and aromatic compounds</topic><topic>Disaccharides - chemical synthesis</topic><topic>Disaccharides - chemistry</topic><topic>Exact sciences and technology</topic><topic>Galectin 3 - antagonists & inhibitors</topic><topic>Ligands</topic><topic>Mass Spectrometry</topic><topic>Molecular Structure</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Protein Binding</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fort, Sébastien</creatorcontrib><creatorcontrib>Kim, Hyo-Sun</creatorcontrib><creatorcontrib>Hindsgaul, Ole</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fort, Sébastien</au><au>Kim, Hyo-Sun</au><au>Hindsgaul, Ole</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Screening for Galectin-3 Inhibitors from Synthetic Lacto-N-biose Libraries Using Microscale Affinity Chromatography Coupled to Mass Spectrometry</atitle><jtitle>Journal of organic chemistry</jtitle><addtitle>J. Org. Chem</addtitle><date>2006-09-15</date><risdate>2006</risdate><volume>71</volume><issue>19</issue><spage>7146</spage><epage>7154</epage><pages>7146-7154</pages><issn>0022-3263</issn><eissn>1520-6904</eissn><coden>JOCEAH</coden><abstract>The synthesis and screening of two β-d-Galp-(1-3)-β-d-GlcpN (lacto-N-biose) disaccharide libraries are reported. Solution-phase synthetic modifications at the HO-2‘ and NH positions were performed in an effort to enhance the affinity toward galectin-3, a galactose-binding protein involved in tumor metastasis, apoptosis, and inflammation. The libraries were screened for galectin-3 binding by microscale frontal affinity chromatography coupled to mass spectrometry (FAC/MS) allowing for rapid ranking of the different inhibitors and the determination of the galectin-3 binding K d's. Compounds bearing a hydrophobic substituent on the NH group showed the highest affinity for the lectin. The N-naphthoyl derivative (K d = 10.6 μM) was the best inhibitor with a 7 times increased affinity as compared to the N-acetyl parent compound (K d = 73.3 μM).</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>16958507</pmid><doi>10.1021/jo060485v</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6133-9900</orcidid></addata></record> |
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| subjects | Acetylglucosamine - analogs & derivatives Acetylglucosamine - chemical synthesis Acetylglucosamine - chemistry Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides Carbohydrates. Nucleosides and nucleotides Chemistry Chromatography, Affinity Condensed benzenic and aromatic compounds Disaccharides - chemical synthesis Disaccharides - chemistry Exact sciences and technology Galectin 3 - antagonists & inhibitors Ligands Mass Spectrometry Molecular Structure Organic chemistry Preparations and properties Protein Binding |
| title | Screening for Galectin-3 Inhibitors from Synthetic Lacto-N-biose Libraries Using Microscale Affinity Chromatography Coupled to Mass Spectrometry |
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