{"id":2831,"date":"2014-08-28T14:48:00","date_gmt":"2014-08-28T13:48:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2831"},"modified":"2026-01-26T16:28:06","modified_gmt":"2026-01-26T16:28:06","slug":"structure-guided-optimization-of-nanomolar-inhibitors-of-the-vhl-hifalpha-protein-protein-interaction","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2014\/08\/28\/structure-guided-optimization-of-nanomolar-inhibitors-of-the-vhl-hifalpha-protein-protein-interaction\/","title":{"rendered":"Structure-guided optimization of nanomolar inhibitors of the VHL-HIFalpha protein-protein interaction"},"content":{"rendered":"<p>Our paper on structure-guided optimization of nanomolar inhibitors of the VHL-HIFalpha protein-protein interaction is now published in J. Med. Chem.<\/p>\n<p>Read our paper\u00a0<a href=\"http:\/\/dx.doi.org\/10.1021\/jm5011258\">on ACS Publications website.<\/a><\/p>\n<div id='gallery-1' class='gallery galleryid-2831 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\/structure-guided-optimization-ToC-.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"441\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-ToC--1024x441.png\" class=\"attachment-large size-large\" alt=\"ToC graphic for on structure-guided optimization of nanomolar inhibitors of the VHL-HIFalpha protein-protein interaction\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-ToC--1024x441.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-ToC--300x129.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-ToC--768x331.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-ToC--1536x662.png 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-ToC--2048x883.png 2048w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon portrait'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-fig1-.png'><img loading=\"lazy\" decoding=\"async\" width=\"1022\" height=\"1024\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-fig1--1022x1024.png\" class=\"attachment-large size-large\" alt=\"Figure 1 on on structure-guided optimization of nanomolar inhibitors of the VHL-HIFalpha protein-protein interaction is now published\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-fig1--1022x1024.png 1022w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-fig1--300x300.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-fig1--150x150.png 150w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-fig1--768x769.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-fig1-.png 1077w\" sizes=\"auto, (max-width: 1022px) 100vw, 1022px\" \/><\/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\/structure-guided-optimization-Fig2-.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"601\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig2--1024x601.png\" class=\"attachment-large size-large\" alt=\"Figure 2. Crystal structure of VBC in complex with ligand 1 (gray carbons, PDB 3ZRC) and 2 (purple carbons, PDB 4W9C)\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig2--1024x601.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig2--300x176.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig2--768x451.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig2-.png 1500w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/structure-guided-optimization-Fig3_0.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"593\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig3_0-1024x593.png\" class=\"attachment-large size-large\" alt=\"Figure 3. Crystal structure of VBC in complex with the ligand 7 (orange carbons, PDB 4W9H)\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig3_0-1024x593.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig3_0-300x174.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig3_0-768x445.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Fig3_0.png 1500w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/structure-guided-optimization-newfigure4.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"671\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-newfigure4-1024x671.png\" class=\"attachment-large size-large\" alt=\"Figure 4. Crystal structure of the VBC in complex with (A) ligand 13 (cyan carbons, PDB 4W9J) with bound HIF-1\u03b1 peptide superposed and (B) ligand 14 (gray carbons, PDB 4W9K)\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-newfigure4-1024x671.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-newfigure4-300x196.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-newfigure4-768x503.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-newfigure4.png 1501w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/structure-guided-optimization-Scheme1.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"444\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Scheme1-1024x444.jpeg\" class=\"attachment-large size-large\" alt=\"Scheme 1. Synthesis of the Ligand 7\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Scheme1-1024x444.jpeg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Scheme1-300x130.jpeg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Scheme1-768x333.jpeg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Scheme1-1536x665.jpeg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/structure-guided-optimization-Scheme1-2048x887.jpeg 2048w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a>\n\t\t\t<\/div><\/figure>\n\t\t<\/div>\n\n","protected":false},"excerpt":{"rendered":"<p>Our paper on structure-guided optimization of nanomolar inhibitors of the VHL-HIFalpha protein-protein interaction is now published in J. Med. Chem. Read our paper\u00a0on ACS Publications website.<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[22,4],"tags":[],"class_list":["post-2831","post","type-post","status-publish","format-standard","hentry","category-22","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2831","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=2831"}],"version-history":[{"count":2,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2831\/revisions"}],"predecessor-version":[{"id":4888,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2831\/revisions\/4888"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=2831"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=2831"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=2831"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}