When not binding to a target’s binding site is better!

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</div> </div> <div class="blog-article-bnr-btm d-flex justify-content-between align-items-center"> <div class="blog-topic-btn"> <a href="https://www.sptlabtech.com/blog/tag/structural-biology" class="topic-btn">Structural Biology</a> <a href="https://www.sptlabtech.com/blog/tag/protein-crystallography" class="topic-btn">Protein Crystallography</a> </div> <div class="blog-article-bnr-links d-flex align-items-center"> <span>Share this blog</span> <ul class="d-flex align-items-center"> <li><a href="http://www.linkedin.com/shareArticle?mini=true&url=https://www.sptlabtech.com/blog/when-not-binding-targets-binding-site-better" target="_blank" rel="noopener"><img src="//www.sptlabtech.com/hubfs/raw_assets/public/SPT-Labtech-2021/SPT-Labtech-Theme-2021/images/linkedin-white.svg" alt=""></a></li> <li><a href="https://twitter.com/intent/tweet?text=I+found+this+interesting+blog+post&url=https://www.sptlabtech.com/blog/when-not-binding-targets-binding-site-better" target="_blank" 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100%);position: absolute;left: 0;right: 0;top: 0;bottom: 0;display: block;content: "";opacity: 0.9;} .blog-article-banner::after {background: linear-gradient(to bottom, rgba(8, 8, 8,0.2) 27%, rgba(62, 40, 77,0.65) 100%);position: absolute;left: 0;right: 0;top: 0;bottom: 0;display: block;content: "";opacity:0.2;} </style></div> <br> <div> <div class="container"> <div id="hs_cos_wrapper_blog_post_audio" class="hs_cos_wrapper hs_cos_wrapper_widget hs_cos_wrapper_type_module" style="" data-hs-cos-general-type="widget" data-hs-cos-type="module"><link rel="stylesheet" href="https://39666904.fs1.hubspotusercontent-na1.net/hubfs/39666904/raw_assets/media-default-modules/master/406/js_client_assets/assets/TrackPlayAnalytics-Cm48oVxd.css"> <link rel="stylesheet" href="https://39666904.fs1.hubspotusercontent-na1.net/hubfs/39666904/raw_assets/media-default-modules/master/406/js_client_assets/assets/Tooltip-DkS5dgLo.css"> <script type="text/javascript"> window.__hsEnvConfig = {"portalID":6586853,"hublet":"na1","hsEnv":"prod","hsDeployed":true,"hsJSRGates":["CMS:JSRenderer:SeparateIslandRenderOption","CMS:JSRenderer:GraphQLQueryBuild","CMS:JSRenderer:MinifyCSS","CMS:JSRenderer:GetServerSideProps","Jsr:DeployLambdasViaCommonAwsAccount","CMS:JSRenderer:LocalProxySchemaVersion1","CMS:JSRenderer:SharedDeps"]}; window.__hsServerPageUrl = "https:\u002F\u002Fwww.sptlabtech.com\u002Fblog\u002Fwhen-not-binding-targets-binding-site-better"; window.__hsBasePath = "\u002Fblog\u002Fwhen-not-binding-targets-binding-site-better"; </script> </div> <div class="blog-article-sec1 bullet-list-points" style="padding-bottom: 20px;"> <span id="hs_cos_wrapper_post_body" class="hs_cos_wrapper hs_cos_wrapper_meta_field hs_cos_wrapper_type_rich_text" style="" data-hs-cos-general-type="meta_field" data-hs-cos-type="rich_text"><p>Most drugs bind to a target’s binding site (orthosteric binding). However, binding to a site distant from the binding site appears to have some very significant advantages over orthosteric binding, one of which is reducing off-target side-effects.</p>  <p>Our latest labCrystal magazine describes an innovative fragment screening strategy to identify potential allosteric drug binding sites of a receptor involved in ion channel diseases, such as Alzheimer’s disease.</p> <p>Published in<span> </span><a href="http://www.pnas.org/content/112/19/E2543.abstract?sid=8257c09a-eb5a-4c2c-ab6f-de3657f58daf" rel="noopener noopener noreferrer" target="_blank">PNAS (Spurny, R<span> </span><em>et al.,<span> </span></em>2015)</a>, this study is part of a collaboration between<span> </span><a href="https://www.kuleuven.be/wieiswie/en/person/00018409" rel="noopener noopener noreferrer" target="_blank">Dr. Ulens, Associate Professor at Katholieke Universiteit (KU)</a><span> </span>Leuven, Belgium, and<span> </span><a href="https://www.janssen.com/belgium/" rel="noopener noopener noreferrer" target="_blank">Janssen Pharma</a>, Belgium<a href="https://www.janssen.com/belgium/" rel="noopener noopener noreferrer" target="_blank"></a>. It uses X-ray crystallography to screen a recently identified chimera (α7-AChBP) of the native α7 nicotinic acetylcholine receptor and the acetylcholine binding protein. Mutations in these receptors result in a diverse range of inherited neurological disorders and form a drug target for a wide variety of therapeutically used drugs, including smoking cessation aids, anti-emetics, sedative/anxiolytic benzodiazepines, barbiturates, general anesthetics and anthelmintics. The PNAS paper reports on the co-crystallization of 5 allosteric binders that produced reproducible crystals.</p> <p>“Thanks to the mosquito crystal’s low pipetting volumes, a larger set of conditions could be screened per complex (on average ~1000 conditions) leading to high-throughput identification of crystallization conditions within 1-2 weeks,” commented Dr. Ulens.</p> <h3><strong>P</strong><strong>ipetting small volumes, fast and reproducibly</strong></h3> <p>X-ray crystallization studies of the allosteric binding complexes were set up using SPT Labtech’s<span> </span><a href="https://www.sptlabtech.com/products/liquid-handling/mosquito-crystal/" rel="noopener" target="_blank">mosquito® crystal</a><span> </span>automated liquid handler to increase speed, throughput and reproducibility.</p> <p><span>Structure determination of the crystals obtained from these screens (Fig 1) resulted in the identification of three allosteric sites of α7-AChBP that were involved in receptor modulation. In combination with electrophysiological recordings on the human α7 nAChR, it was demonstrated that fragment binding at these sites modulated receptor function.</span></p> <p><img src="https://www.sptlabtech.com/hs-fs/hubfs/Campaigns/Drug-Discovery/DD000%20-%20Legacy%20blog%20assets/When%20not%20binding%20to%20a%20target%E2%80%99s%20binding%20site%20is%20better/DD000-labcrystal-crystallography-body-2.gif?width=1000&name=DD000-labcrystal-crystallography-body-2.gif" alt="DD000-labcrystal-crystallography-body-2" width="1000" style="width: 1000px;" loading="lazy" srcset="https://www.sptlabtech.com/hs-fs/hubfs/Campaigns/Drug-Discovery/DD000%20-%20Legacy%20blog%20assets/When%20not%20binding%20to%20a%20target%E2%80%99s%20binding%20site%20is%20better/DD000-labcrystal-crystallography-body-2.gif?width=500&name=DD000-labcrystal-crystallography-body-2.gif 500w, https://www.sptlabtech.com/hs-fs/hubfs/Campaigns/Drug-Discovery/DD000%20-%20Legacy%20blog%20assets/When%20not%20binding%20to%20a%20target%E2%80%99s%20binding%20site%20is%20better/DD000-labcrystal-crystallography-body-2.gif?width=1000&name=DD000-labcrystal-crystallography-body-2.gif 1000w, https://www.sptlabtech.com/hs-fs/hubfs/Campaigns/Drug-Discovery/DD000%20-%20Legacy%20blog%20assets/When%20not%20binding%20to%20a%20target%E2%80%99s%20binding%20site%20is%20better/DD000-labcrystal-crystallography-body-2.gif?width=1500&name=DD000-labcrystal-crystallography-body-2.gif 1500w, https://www.sptlabtech.com/hs-fs/hubfs/Campaigns/Drug-Discovery/DD000%20-%20Legacy%20blog%20assets/When%20not%20binding%20to%20a%20target%E2%80%99s%20binding%20site%20is%20better/DD000-labcrystal-crystallography-body-2.gif?width=2000&name=DD000-labcrystal-crystallography-body-2.gif 2000w, https://www.sptlabtech.com/hs-fs/hubfs/Campaigns/Drug-Discovery/DD000%20-%20Legacy%20blog%20assets/When%20not%20binding%20to%20a%20target%E2%80%99s%20binding%20site%20is%20better/DD000-labcrystal-crystallography-body-2.gif?width=2500&name=DD000-labcrystal-crystallography-body-2.gif 2500w, https://www.sptlabtech.com/hs-fs/hubfs/Campaigns/Drug-Discovery/DD000%20-%20Legacy%20blog%20assets/When%20not%20binding%20to%20a%20target%E2%80%99s%20binding%20site%20is%20better/DD000-labcrystal-crystallography-body-2.gif?width=3000&name=DD000-labcrystal-crystallography-body-2.gif 3000w" sizes="(max-width: 1000px) 100vw, 1000px"></p> <p><em><strong>Fig 1. A 200 nanoliter sitting drop pipetted by mosquito crystal, containing two crystals used for actual diffraction data collection.</strong></em></p> <p> </p> <p> </p></span> </div> </div> </div> <div data-global-resource-path="SPT-Labtech-2021/SPT-Labtech-Theme-2021/templates/partials/footer.html"><footer class="footer"> <div class="container"> <div class="container-fluid footer-inr"> <div class="row-fluid-wrapper"> <div class="row-fluid"> <div class="span12 widget-span widget-type-cell " style="" data-widget-type="cell" data-x="0" data-w="12"> <div class="row-fluid-wrapper row-depth-1 row-number-1 dnd-section"> <div class="row-fluid "> <div class="span12 widget-span widget-type-cell dnd-column" style="" data-widget-type="cell" data-x="0" data-w="12"> <div class="row-fluid-wrapper row-depth-1 row-number-2 dnd-row"> <div class="row-fluid "> <div class="span12 widget-span widget-type-custom_widget dnd-module" style="" data-widget-type="custom_widget" data-x="0" data-w="12"> <div id="hs_cos_wrapper_widget_1727255406258" class="hs_cos_wrapper hs_cos_wrapper_widget hs_cos_wrapper_type_module" style="" data-hs-cos-general-type="widget" data-hs-cos-type="module"><footer class="footer"> <div class="footer-top"> <img src="https://www.sptlabtech.com/hubfs/Admin/Logos/SPT%20Labtech%20Logo.png" alt="Logo" class="footer-logo"> </div> <div class="footer-line"></div> <div class="footer-nav"> <a href="https://www.sptlabtech.com/products">Products</a> <a href="https://www.sptlabtech.com/company">Company</a> <a href="https://www.sptlabtech.com/culture">Culture</a> <a href="https://apply.workable.com/spt-labtech/">Careers</a> <a href="https://www.sptlabtech.com/resources">Resources</a> <a href="https://www.sptlabtech.com/product-inquiry">Contact</a> <a href="https://store.sptlabtech.com/">Shop</a> </div> <div class="footer-line"></div> <div class="footer-bottom"> <div class="column column-left"> <p style="font-size: 20px;"><strong>Subscribe to get our latest update</strong></p> <button class="subscribe-button" id="subscribeButton">Subscribe</button> </div> <div class="column column-right"> <p style="font-size: 20px;"> <strong>Follow Us</strong></p> <div class="social-icons"> <a href="https://www.linkedin.com" target="_blank"> <img src="https://www.sptlabtech.com/hubfs/Quantifoil%20Website/Admin%20only/Logos/Teal%20LinkedIn%20Logo%20Icon%20PNG.png.png" alt="LinkedIn"> </a> <a href="https://www.twitter.com" target="_blank"> <img src="https://www.sptlabtech.com/hubfs/Twitter%20-%20X%20New%20logo.png" alt="X"> </a> </div> </div> </div> <div class="footer-final"> <div> <a href="https://www.sptlabtech.com/privacy">Privacy Policy</a> <a href="https://www.sptlabtech.com/legal">Legal</a> </div> <div class="footer-date"> <p>© 2024 SPT Labtech Ltd</p> </div> </div> </footer>  <div id="popupForm" class="popup"> <div class="popup-content"> <span class="close-btn" id="closePopup"></span>  <span id="hs_cos_wrapper_widget_1727255406258_" class="hs_cos_wrapper hs_cos_wrapper_widget hs_cos_wrapper_type_form" style="" data-hs-cos-general-type="widget" data-hs-cos-type="form"><h3 id="hs_cos_wrapper_form_920571762_title" class="hs_cos_wrapper form-title" data-hs-cos-general-type="widget_field" data-hs-cos-type="text"></h3> <div id="hs_form_target_form_920571762"></div> </span> </div> </div></div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </footer></div>  <script defer src="/hs/hsstatic/content-cwv-embed/static-1.1293/embed.js"></script> <script src="https://www.sptlabtech.com/hs-fs/hub/6586853/hub_generated/template_assets/85829631861/1690760505242/SPT-Labtech-2021/SPT-Labtech-Theme-2021/js/compiled.min.js"></script> <script> var hsVars = hsVars || {}; 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When not binding to a target’s binding site is better!