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Ciulli Laboratory

School of Life Sciences, University of Dundee

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Chemical & Structural Biology of Protein-Protein Interactions

We are broadly interested with understanding and exploiting the ligandability of protein-protein interactions (PPIs) and protein surfaces within complex biological systems. Of particular interest are protein interfaces recognizing protein Post-Translational Modifications (PTMs). We employ a question-driven, multi-disciplinary approach that combines chemical, biophysical and structural techniques with the concepts of fragment-based drug design. Current research efforts are directed towards targeting PPIs and PTM recognition within protein families of biological and medical relevance within the Ubiquitin and Chromatin systems:

1) the Cullin RING E3 ubiquitin ligases (CRLs) multisubunit complexes

2) a family of multidomain proteins containing paired chromatin reader domains

We seek to understand the chemical nature of the surfaces and intersubunit interfaces of these proteins, and to exploit their tractability and selectivity toward small molecule modulation. The ‘chemical probes’ we design and develop are evaluated biophysically, structurally and inside living cells as tools to address biological questions.

  • Electron density map of a small-molecule ligand bound to a protein
  • Dissecting fragment-based lead discovery at protein-protein interfaces
  • A drug bound to its protein target
  • Targeting multi-protein complexes with small molecules
  • Protein-protein interfaces: Molecular insights
  • Biophysical approaches to study protein-ligand and protein-protein interactions
  • A fragment bound to its target binding site
  • Investigating the activity of our chemical probes inside living cells

Latest News

  • Conner
    Welcome to Conner, who joins the group for his final Year-1 rotation project as part of the MRC-DTP programme
  • n→π* interaction in prolines and VHL inhibitors
    New paper: Thioamide substitution to probe the hydroxyproline recognition of VHL ligands published in Bioorg Med Chem
  • ToC graphics
    Our paper probing the ligandability of PHD finger domains of BAZ2A and BAZ2B by fragment screening is now published in ACS Chem Biol
  • ToC graphics
    New paper: Refinement of the “Bump-and-Hole” Approach to Allele-Selective BET Bromodomain Inhibition now published in Chemical Science

Funding

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Prof Alessio Ciulli
Professor of Chemical and Structural Biology
School of Life Sciences, University of Dundee
Division of Biological Chemistry & Drug Discovery
James Black Centre
Dow Street, Dundee, DD1 5EH
United Kingdom

E-mail: a.ciulli@dundee.ac.uk
Tel: +44 (0)1382 386230
Fax: +44 (0)1382 386373

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