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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

  • Wojciech 'Jay' Stec
    Welcome to Jay who starts as new postdoc in the group
  • ToC graphics
    Our new paper describing an SPR kinetic assay to monitor PROTAC ternary complexes is now out in ACS Chemical Biology
  • Alessandra Cipriano
    Welcome to Alessandra who joins the group as a visiting PhD student from the University of Salerno, Italy
  • ToC graphics
    Our latest paper describing novel fluorinated VHL ligands as spy molecules for 19F NMR screening is out in Chemical Communications

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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