BMERC Seminar: Targeting Protein-Protein Interactions and Surfaces of E3 Cullin RING Ubiquitin Ligases with Chemical Probes

BMERC Seminar

When:       Monday, September 21, 2 pm

Where:      ENG room 203, 44 Cummington Street

Title:          Targeting Protein-Protein Interactions and Surfaces of E3 Cullin RING Ubiquitin Ligases with Chemical Probes: Small Molecule Inhibitors and PROTACs

Speaker:  Dr. Alessio Ciulli

Principal Investigator, Reader and BBSRC David Phillips Fellow at the School of Life Sciences, University of Dundee

Dr. Ciulli received his Ph.D. from Cambridge University, and conducted post-doctoral research there with Professors Chris Abell and Sir Tom Blundell on fragment-based and structure-based drug design. In 2013 he moved his laboratory to Dundee where he took up a Readership (Associate Professorship) in Chemical & Structural Biology. 

Abstract: This talk will focus on developing and characterizing small molecules binders of Cullin RING E3 Ubiquitin Ligases (CRLs) – the largest family of multisubunit ubiquitylating enzymes. CRL-targeting chemical probes can be used in their own right as E3 ligase inhibitors or modulators of the biological pathway in which the specific CRL is involved. In addition, CRL-targeting ligands can be suitably tethered with a ligand for a given protein of interest, yielding bifunctional proteolysis targeting chimeras (PROTACs) to hijack the ubiquitin proteasome system and induce the intracellular degradation of the target protein. I will describe recent progress from the lab with potent and selective VHL inhibitors and their applications in each of those areas, as well as current efforts at probing ligandability of CRLs using fragment-based and peptide-based approaches.

References:

Galdeano C. et al. J. Med. Chem. 2014, 57 (20), 8657-8663.

Bulatov E., Ciulli A. Biochem. J., 2015, 467, 365-386.

Zengerle M. et al. ACS Chem. Biol., 2015, 10 (8), 1770-1777.