{"id":2886,"date":"2018-06-27T17:10:00","date_gmt":"2018-06-27T16:10:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2886"},"modified":"2024-01-11T17:21:39","modified_gmt":"2024-01-11T17:21:39","slug":"introducing-3-fluoro-4-hydroxyprolines","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2018\/06\/27\/introducing-3-fluoro-4-hydroxyprolines\/","title":{"rendered":"Introducing 3-Fluoro-4-hydroxyprolines"},"content":{"rendered":"<p><\/p>\n\n\n<p>Introducing 3-Fluoro-4-hydroxyprolines: Synthesis, conformational analysis and stereoselective recognition by VHL E3 ligase for protein degradation.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>@EndriuT developed diverse synthetic routes to achieve all four diastereoisomers of unprecedented unnatural fluorinated analogues of 4-hydroxyproline (Hyp) &#8211; the most common posttranslationally modified aminoacid<\/li>\n\n\n\n<li>with @_xavierlucas_ et al demonstrate using small-mol NMR, crystallography and modelling how fluorination affects the conformational preferences and H-bond capacity of the Hyp core: fluorination in F-Hyps inverts the natural preference from the C4-exo to the C4-endo pucker<\/li>\n\n\n\n<li>using ITC they show that the VHL E3 ligase, which naturally recognizes C4-exo Hyp, still binds to F-Hyp-containing HIF peptides and VHL ligands &#8211; in a stereoselective fashion, which they rationalised by means of co-crystal structures and electrostatic potential calculations<\/li>\n\n\n\n<li>a #PROTAC degrader containing the weak-affinity epimer of F-Hyp induced highly selective degradation of the target protein (Brd4) at concentrations much lower than the binary Kd for VHL<\/li>\n\n\n\n<li>An important first step to expand the chemical space of VHL-based degrader molecules, with potential to fine-tune their PK properties and specificity too<\/li>\n<\/ul>\n\n\n\n<p>Very proud of Lab\u2019s work just out in\u00a0<a href=\"https:\/\/pubs.acs.org\/journal\/jacsat\">@JACS<\/a>\u00a0by\u00a0<a href=\"http:\/\/www.lifesci.dundee.ac.uk\/groups\/alessio-ciulli\/\/group\/ciulli-lab-dundee\/andrea-testa\">Andrea<\/a>,\u00a0<a href=\"http:\/\/www.lifesci.dundee.ac.uk\/groups\/alessio-ciulli\/\/group\/ciulli-lab-dundee\/xavier-lucas\">Xavi<\/a>\u00a0and coworkers!\u00a0well done everyone at @UoDLifeSciences and beyond, and thanks to @ERC_Research @MSCActions for funding<\/p>\n\n\n\n<p><a href=\"https:\/\/pubs.acs.org\/doi\/abs\/10.1021\/jacs.8b05807\">Read our article Open Access<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Introducing 3-Fluoro-4-hydroxyprolines: Synthesis, conformational analysis and stereoselective recognition by VHL E3 ligase for protein degradation. Very proud of Lab\u2019s work just out in\u00a0@JACS\u00a0by\u00a0Andrea,\u00a0Xavi\u00a0and coworkers!\u00a0well done everyone at @UoDLifeSciences and beyond, and thanks to @ERC_Research @MSCActions for funding Read our article Open Access.<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18,4],"tags":[],"class_list":["post-2886","post","type-post","status-publish","format-standard","hentry","category-18","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2886","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=2886"}],"version-history":[{"count":0,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2886\/revisions"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=2886"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=2886"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=2886"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}