CINXE.COM

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<p><strong>Stapled peptides</strong> are synthetic 'mini-proteins' that are locked into their bioactive α-helical secondary structure, so conferring high specificity, high potency and resistance to enzymatic degradation. They target protein-protein interactions (PPIs), opening up a range of targets that were previously considered to be undruggable.</p> <div class="tabbed_content"> <div class="tab_menu"> <div class="tab tab_1 tab_open" data-tab="1" data-tabname="products" id="pharm_tabs_products"> <span>Products</span></div> <div class="tab tab_2" data-tab="2" data-tabname="background" id="pharm_tabs_background"><span>Background</span> </div> </div> <div class="tab_content tab_1 tab_open" data-tab="1"> <div class="pharm_products"><table class="pharm_prod_table table table-condensed"> <tr> <th>Cat. No.</th> <th>Product Name / Activity</th> </tr> <tr> <td>6531</td> <td><a href="/products/nls-stax-h_6531" title="View price & availability information for NLS-StAx-h">NLS-StAx-h</a></td> </tr> <tr class="pharm_prod_table_action"> <td></td><td>Wnt signaling inhibitor; inhibits β-catenin-transcription factor interactions</td> </tr> <tr> <td>6477</td> <td><a href="/products/sahm1_6477" title="View price & availability information for SAHM1">SAHM1</a></td> </tr> <tr class="pharm_prod_table_action"> <td></td><td>Notch pathway inhibitor; prevents Notch complex assembly</td> </tr></table></div> </div> <div class="tab_content tab_2" data-tab="2"> <p>Peptides are an alternative class of drug molecule, which are being used to therapeutically target previously undruggable protein-protein interactions (PPIs). The interacting surfaces of PPIs are shallow/flat, large and non-hydrophobic making them ideal targets for peptides, which are able to mimic a native protein. Peptides are highly selective, but often suffer from poor cell permeability, plasma stability and bioavailability.</p> <p>Stapling a peptide overcomes these limitations by the formation of a synthetic mini-protein, which is locked into a bioactive α-helical secondary structure by site-specific insertion of a chemical 'brace'. Chemical restriction of conformation in this way improves the pharmacological properties of peptides. Stapled peptides possess:</p> <ul> <li>Increased potency due to stabilization of favorable binding conditions</li> <li>Decreased enzymatic degradation due to blockade of protease active sites</li> <li>Improved selectivity for intended target decreasing off-target effects</li> <li>Improved affinity on an atomic level without requiring additional interactions</li> </ul> <p>Targeting protein-protein interactions (PPIs) with stapled peptides opens an expanded range of targets for therapeutic intervention, which were previously considered to be undruggable. Transcription factors which were thought to be undruggable have been successfully inhibited by stapled peptides; for example, ALRN-6924 is under clinical development as an anti-cancer drug targeting HDM2/p53. Stapled peptides have also been designed to disrupt enzymes, multidrug resistance efflux pumps and membrane receptor dimers.</p> </div> <div class="tab_content tab_3" data-tab="3"> </div> <div class="tab_content tab_4" data-tab="4"> </div> <div class="tab_content tab_5" data-tab="5"> </div> <div class="tab_content tab_6" data-tab="6"> </div> </div> </div> <div id="sidebar" class="col-xs-12 col-sm-4 col-md-3 col-lg-3 col-xl-3"> <div class="resources_sidebar_container"> <div class="fp_four_box"> <div class="fp_box_wrapper"><h3>Featured New Products</h3> <div class="fp_featured_product"><a href="https://www.tocris.com/products/corafluortm-1-haloalkane_8817">8817 | CoraFluor™ 1, Haloalkane</a><br /> Cell impermeable terbium cryptate FRET donor for TR-FRET assay development, with chloroalkane ligand</div> <div class="fp_featured_product"><a href="https://www.tocris.com/products/hb-2-30_8831">8831 | HB-2-30</a><br /> Fluorescent TG2/LRP1 substrate for imaging endocytosis</div> <div 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