{"id":2168,"date":"2020-10-15T10:50:00","date_gmt":"2020-10-15T09:50:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2168"},"modified":"2026-01-26T16:28:03","modified_gmt":"2026-01-26T16:28:03","slug":"introducing-bromotag-and-agb1","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2020\/10\/15\/introducing-bromotag-and-agb1\/","title":{"rendered":"Introducing BromoTAG and AGB1"},"content":{"rendered":"

Introducing BromoTAG and AGB1: our new inducible degron system for potent, rapid, selective protein degradation<\/p>\n

Great work by\u00a0Adam\u00a0and\u00a0Conner, who led chemistry and biology on this study, and in collaboration\u00a0with Dario Alessi\u2019s\u00a0group<\/a>!\u00a0<\/p>\n

Read the Open Access full article.<\/a><\/p>\n

Authors<\/strong>: Adam G. Bond, Conner Craigon, Kwok-Ho Chan, Andrea Testa, Athanasios Karapetsas, Rotimi Fasimoye, Thomas Macartney, J. Julian Blow, Dario R. Alessi, and Alessio Ciulli*<\/p>\n

Title<\/strong>: Development of BromoTag: A \u201cBump-and-Hole\u201d\u2013PROTAC System to Induce Potent, Rapid, and Selective Degradation of Tagged Target Proteins<\/p>\n

Abstract<\/strong><\/h2>\n

Small-molecule-induced protein depletion technologies, also called inducible degrons, allow degradation of genetically engineered target proteins within cells and animals. Here, we design and develop the BromoTag, a new inducible degron system comprising a Brd4 bromodomain L387A variant as a degron tag that allows direct recruitment by heterobifunctional bumped proteolysis targeting chimeras (PROTACs) to hijack the VHL E3 ligase. We describe extensive optimization and structure\u2013activity relationships of our bump-and-hole\u2013PROTACs using a CRISPR knock-in cell line expressing model target BromoTag-Brd2 at endogenous levels. Collectively, our cellular and mechanistic data qualifies bumped PROTAC AGB1 as a potent, fast, and selective degrader of BromoTagged proteins, with a favorable pharmacokinetic profile in mice. The BromoTag adds to the arsenal of chemical genetic degradation tools allowing us to manipulate protein levels to interrogate the biological function and therapeutic potential in cells and in vivo.<\/p>\n

Our PROTAC degrader AGB1 and BromoTAG-specific antibody are available with no strings-attached upon request. Feel free to contact\u00a0Alessio<\/a>\u00a0if you\u2019d like to try the BromoTag out with your favourite protein!\u00a0<\/p>\n

Related links<\/h2>\n