{"id":2188,"date":"2021-06-06T11:47:00","date_gmt":"2021-06-06T10:47:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2188"},"modified":"2026-01-26T16:28:03","modified_gmt":"2026-01-26T16:28:03","slug":"estimating-the-cooperativity-of-protac","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2021\/06\/06\/estimating-the-cooperativity-of-protac\/","title":{"rendered":"Estimating the cooperativity of PROTAC"},"content":{"rendered":"<p>New preprint: Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay<\/p>\n<p>Great work by Gugi.<\/p>\n<p><a href=\"https:\/\/doi.org\/10.33774\/chemrxiv-2021-zj19k\">Read the pre-print article<\/a><\/p>\n<p><strong>Authors:<\/strong>\u00a0Guilherme Castro, Alessio Ciulli*<\/p>\n<p><strong>Title:<\/strong>\u00a0Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay<\/p>\n<h2 class=\"wp-block-heading\"><strong>Abstract<\/strong><\/h2>\n<p>Cooperativity is an important parameter to understand the ternary complexes formed by protein degraders. We developed fluorine NMR competition binding experiments to determine cooperativity of PROTACs. We show applicability to estimate both positive and negative cooperativity, also with homo-dimerizers, and highlight key features and considerations for optimal assay development.<\/p>\n<div id='gallery-1' class='gallery galleryid-2188 gallery-columns-3 gallery-size-large'><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/ToC-01-PROTAC-induced-ternary-19F-NMR-1.png'><img loading=\"lazy\" decoding=\"async\" width=\"945\" height=\"472\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/ToC-01-PROTAC-induced-ternary-19F-NMR-1.png\" class=\"attachment-large size-large\" alt=\"ToC Graphic for article Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-2-scaled.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"866\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-2-scaled.jpg\" class=\"attachment-large size-large\" alt=\"Figure 1. General setup of the competitive 19F NMR assay to determine cooperativity\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-3-scaled.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"561\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-3-scaled.jpg\" class=\"attachment-large size-large\" alt=\"Scheme 1. Structures of 19F NMR VHL spy molecule 19 and PROTACs MZ1, MZP-54, MZP-55 and MZP-61\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-4-scaled.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"777\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-4-scaled.jpg\" class=\"attachment-large size-large\" alt=\"Scheme 1. Structures of 19F NMR VHL spy molecule 19 and PROTACs MZ1, MZP-54, MZP-55 and MZP-61\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-5-scaled.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"342\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-5-scaled.jpg\" class=\"attachment-large size-large\" alt=\"Scheme 3. Structures of 19F NMR VHL spy molecules 7 and 18.\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-6-scaled.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"762\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-6-scaled.jpg\" class=\"attachment-large size-large\" alt=\"Figure 3. F19 transverse relaxation times of spy molecules\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-7.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"502\" height=\"502\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-7.jpg\" class=\"attachment-large size-large\" alt=\"Figure 4. Evaluation of a weaker VHL-targeting PROTAC\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-7.jpg 502w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-7-150x150.jpg 150w\" sizes=\"auto, (max-width: 502px) 100vw, 502px\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-8.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"567\" height=\"567\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-8.jpg\" class=\"attachment-large size-large\" alt=\"Figure 5. Evaluation of VHL homo-PROTACs\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-8.jpg 567w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/PROTAC-induced-ternary-19F-NMR-8-150x150.jpg 150w\" sizes=\"auto, (max-width: 567px) 100vw, 567px\" \/><\/a>\n\t\t\t<\/div><\/figure>\n\t\t<\/div>\n\n","protected":false},"excerpt":{"rendered":"<p>New preprint: Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay Great work by Gugi. Read the pre-print article Authors:\u00a0Guilherme Castro, Alessio Ciulli* Title:\u00a0Estimating the cooperativity of PROTAC-induced ternary complexes using 19F NMR displacement assay Abstract Cooperativity is an important parameter to understand the ternary complexes formed by protein degraders. We developed [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[14,4],"tags":[],"class_list":["post-2188","post","type-post","status-publish","format-standard","hentry","category-14","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2188","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/comments?post=2188"}],"version-history":[{"count":2,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2188\/revisions"}],"predecessor-version":[{"id":4846,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2188\/revisions\/4846"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=2188"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=2188"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=2188"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}