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Anchoring ligandable binding sites at E3 ligase surfaces for plug-and-play PROTACs.

Total Cost €


EC-Contrib. €






Project "ANCHOR E3s" data sheet

The following table provides information about the project.


Organization address
address: Nethergate
city: DUNDEE
postcode: DD1 4HN

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-08-01   to  2018-07-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF DUNDEE UK (DUNDEE) coordinator 183˙454.00


 Project objective

The Anchor E3s project proposes to establish, for the first time, an efficient protocol for the discovery and characterisation of accessible binding sites at any patch of a protein surface, regardless of its involvement in biological function. One of the motivation of the research is to develop a general approach to discover new “anchor” ligands that can enable improved plug-and-play proteolysis targeting chimeras (PROTACs) as chemical degraders of any protein of interest. The project will build on results from the host lab who identified a series of low molecular-weight fragments addressing novel patches at the surface of Cullin RING E3 ubiquitin ligases (CRLs) with currently unknown functionality, demonstrating that accessible and “ligandable” binding sites can be found on CRL surfaces. A combination of structure-based computational techniques informed by biophysical experiments and X-ray crystallography will be used to reveal, characterise, and target new ligandable binding sites at CRL surfaces. Promising anchor fragments will then be identified and grown into suitable binders, and eventually linked to assemble novel PROTACs, which will be assessed in cellular assays. The ultimate goal of the research is to develop and establish the PROTAC approach as an efficient and universal chemical biology platform for target validation, regardless of the perceived “druggability” of the targeted protein.


year authors and title journal last update
List of publications.
2018 Xavier Lucas, Inge Van Molle, Alessio Ciulli
Surface Probing by Fragment-Based Screening and Computational Methods Identifies Ligandable Pockets on the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase
published pages: 7387-7393, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.8b00842
Journal of Medicinal Chemistry 61/16 2019-06-13
2017 Alessio Bortoluzzi, Anastasia Amato, Xavier Lucas, Manuel Blank, Alessio Ciulli
Structural basis of molecular recognition of helical histone H3 tail by PHD finger domains
published pages: 1633-1651, ISSN: 0264-6021, DOI: 10.1042/BCJ20161053
Biochemical Journal 474/10 2019-06-13
2017 Morgan S Gadd, Andrea Testa, Xavier Lucas, Kwok-Ho Chan, Wenzhang Chen, Douglas J Lamont, Michael Zengerle, Alessio Ciulli
Structural basis of PROTAC cooperative recognition for selective protein degradation
published pages: 514-521, ISSN: 1552-4450, DOI: 10.1038/nchembio.2329
Nature Chemical Biology 13/5 2019-06-13
2018 Anastasia Amato, Xavier Lucas, Alessio Bortoluzzi, David Wright, Alessio Ciulli
Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach
published pages: 915-921, ISSN: 1554-8929, DOI: 10.1021/acschembio.7b01093
ACS Chemical Biology 13/4 2019-06-13
2018 Pedro Soares, Xavier Lucas, Alessio Ciulli
Thioamide substitution to probe the hydroxyproline recognition of VHL ligands
published pages: 2992-2995, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2018.03.034
Bioorganic & Medicinal Chemistry 26/11 2019-06-13
2017 Xavier Lucas, Alessio Ciulli
Recognition of substrate degrons by E3 ubiquitin ligases and modulation by small-molecule mimicry strategies
published pages: 101-110, ISSN: 0959-440X, DOI: 10.1016/
Current Opinion in Structural Biology 44 2019-06-13
2018 Andrea Testa, Xavier Lucas, Guilherme V. Castro, Kwok-Ho Chan, Jane E. Wright, Andrew C. Runcie, Morgan S. Gadd, William T. A. Harrison, Eun-Jung Ko, Daniel Fletcher, Alessio Ciulli
3-Fluoro-4-hydroxyprolines: Synthesis, Conformational Analysis, and Stereoselective Recognition by the VHL E3 Ubiquitin Ligase for Targeted Protein Degradation
published pages: 9299-9313, ISSN: 0002-7863, DOI: 10.1021/jacs.8b05807
Journal of the American Chemical Society 140/29 2019-06-13

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