University of Dundee

Professor Alessio Ciulli FRSC

Chemical and Structural Biology of Protein-Protein Interactions
Professor of Chemical and Structural Biology
School of Life Sciences, University of Dundee, Dundee
Full Telephone: 
+44 (0) 1382 386230, int ext 86230


Research in the Ciulli Lab broadly spans the fields of Chemical Biology and Structural Biology of Protein-Protein Interactions (PPIs) and is specifically concerned with studies of druggability of PPIs to small molecule modulators. Of particular interest are protein surfaces and interfaces recognizing protein Post-Translational Modifications (PTMs) within multi-domain and multi-subunit protein complexes. We employ a question-driven, multi-disciplinary approach that combines chemical, biophysical and structural techniques with the concepts and approaches of fragment-based and structure-based drug design. The 'chemical probes' we design and develop are evaluated biophysically, structurally and whenever possible within living cells as tools to address biological questions, and as starting leads with potential to be developed as novel therapeutics.

Current and future research efforts are directed towards targeting PPIs and PTM recognition within two protein families of biological and medical relevance:

Ubiquitin System: the Cullin RING E3 ubiquitin ligases (CRLs) multisubunit complexes
Chromatin System: Multidomain proteins of containing paired domains of the epigenetic reader families


BS42011:  A 4th year mocule entitled "Advanced Organic Chemistry and Chemical Biology"


1.  Cardote, T.A.F., and Ciulli, A.  Cyclic and macrocyclic peptides as chemical tools to recognise protein surfaces and probe protein-protein interactions. ChemMedChem, Publication Date (Web): Nov 13, 2015. DOI: 10.1002/cmdc.201500450
(Read Online) 

 2.  Baud, M.G.J., Lin-Shiao, E., Zengerle, M., Tallant, C., and Ciulli A. New synthetic routes to triazolo-benzodiazepine analogues: expanding the scope of the bump-and-hole approach for selective BET bromodomain inhibition. J. Med. Chem., Article ASAP, Publication Date (Web): September 14, 2015. DOI: 10.1021/acs.jmedchem.5b01135
(Read Online) 

 3.  Gadd, M.S., Bulatov, E. and Ciulli, A. Serendipitous SAD solution for DMSO-soaked SOCS2-ElonginC-ElonginB crystals using covalently incorporated dimethylarsenic: insights into substrate receptor conformational flexibility in Cullin RING ligases. Plos One 2015, June 29; 10(6):e013218
(Read Online) 

4.  Zengerle, M., Chan, K.-H., Ciulli, A. Selective small molecules induced degradation of the BET bromodomain protein BRD4. ACS Chem. Biol. 2015, 10(8), 1770-1888
(Read Online)

5.  Bulatov, E., Ciulli, A. Targeting Cullin RING E3 ubiquitin ligases for drug discovery: structure, assembly and small molecule modulation. Biochem. J. 2015, 467(3), 365–386.
(Read Online)

6.  Tallant, C., Valentini, E. Fedorov, O., Overvoorde, L., Ferguson, F.M., Filippakopoulos, P., Svergun, D.I., Knapp, S., Ciulli, A. Molecular basis of histone tail recognition by human TIP5 PHD finger and Bromodomain of the chromatin remodelling complex NoRC.Structure, 2015, 23 (1), 80-92  (Read Online)

7.  Bulatov, E., Martin, E.M., Chatterjee, S., Knebel, A., Shimamura, S., Konijnenberg, A., Johnson, C., Zinn, N., Grandi, P., Sobott, F., Ciulli, A. Biophysical studies on interactions and assembly of full-size E3 ubiquitin ligase: suppressor of cytokine signaling 2 (SOCS2):ElonginBC:Cullin5:RING-box protein 2 (Rbx2). J. Biol. Chem. 2015, 290(7) 4178-4198. [Epub ahead of print] (Read Online)

8.  Baud, M.G., Lin-Shiao, E., Cardote, T., Tallant, C., Pschibul, A., Chan, K.H., Zengerle, M., Garcia, J.R., Kwan, T.T., Ferguson, F.M., Ciulli, A. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes.
Science 2014, 346 (6209), 638-641 (Read Online)

9.  Galdeano, C., Gadd, M.S., Soares, P., Scaffidi, S., Van Molle, I., Birced, I., Hewitt, S., Dias, D.M., Ciulli A. Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with In Vitro Nanomolar Affinities
J. Med Chem. 2014, 57 (20), 8657-8663. (Read Online)

10. Dias, D.M., Van Molle, I., Baud, M.G.J., Galdeano, C., Geraldes, C.F.G.C., Ciulli, A. Is NMR Fragment Screening Fine-Tuned to Assess Druggability of Protein-Protein Interactions?
ACS Med. Chem. Lett. 2014, 5 (1), 23-28. (Read Online)

11. Thomas, J.C., Matak-Vinkovic, D., Van Molle, I., Ciulli, A. Multimeric Complexes among Ankyrin-Repeat and SOCS-box Protein 9 (ASB9), ElonginBC, and Cullin 5: Insights into the Structure and Assembly of ECS-type Cullin-RING E3 Ubiquitin Ligases. Biochemistry 2013, 52(31), 5236-5246. (Read online)

12. Silvestre, H.L., Blundell, T.L., Abell, C., Ciulli, A. Integrated biophysical approach to fragment screening and validation for fragment-based lead discovery. Proc. Natl. Acad. Sci. U.S.A. 2013, 110(32), 12984-12989. (Read online)

13. Ciulli, A. Biophysical Screening for the Discovery of Small-Molecule Ligands, in: ‘Protein-Ligand Interactions - Methods and Applications, 2nd Ed.’. T. Daviter and M. Williams, Ed., Springer Protocols, Humana Press. ISBN: 978-1-62703-397-8 Methods Mol Biol. 2013, vol. 1008, pp. 357-388. (Read online)

14. Van Molle, I., Thomann, A., Buckley, D.L., So, E.C., Lang, S., Crews, C.M., Ciulli, A. Dissecting fragment-based lead discovery at the von-Hippel Lindau protein : Hypoxia Inducible Factor 1α protein-protein interface. Chem. Biol. 2012, 19, 1300-1312. (Read online)