{"id":7113,"date":"2025-04-10T11:30:17","date_gmt":"2025-04-10T03:30:17","guid":{"rendered":"https:\/\/molchanges.com\/?page_id=7113"},"modified":"2025-07-07T16:19:29","modified_gmt":"2025-07-07T08:19:29","slug":"stapled-peptides","status":"publish","type":"page","link":"https:\/\/molchanges.com\/zh\/stapled-peptides","title":{"rendered":"\u9489\u80bd"},"content":{"rendered":"
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Although stapled \u03b1-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility\/behavior, optimization of C-terminal length\/helicity to enhance potency, and optimization of staple type\/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects (\u2009>\u20093800x on-target index). Application of these \u2018design rules\u2019 to a distinct Mdm2(X) peptide series improves (\u2009>\u2009150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.<\/p><\/div><\/div>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Peptide Modifications Stapled Peptides The all-carbon scaffold has an \u03b1-helical structure of the polypeptide, and the all-carbon scaffold stabilizes the \u03b1-helical structure and enhances the interaction between the polypeptide molecule and the protein. What is Stapled Peptides? Studies have shown that peptides with \u03b1-helical structure and rich in positive charge can cross cell membranes. However, […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-7113","page","type-page","status-publish","hentry"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/molchanges.com\/zh\/wp-json\/wp\/v2\/pages\/7113","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/molchanges.com\/zh\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/molchanges.com\/zh\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/molchanges.com\/zh\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/molchanges.com\/zh\/wp-json\/wp\/v2\/comments?post=7113"}],"version-history":[{"count":0,"href":"https:\/\/molchanges.com\/zh\/wp-json\/wp\/v2\/pages\/7113\/revisions"}],"wp:attachment":[{"href":"https:\/\/molchanges.com\/zh\/wp-json\/wp\/v2\/media?parent=7113"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}