Universiteit Leiden

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Protein Surface Recognition Using Designed Molecules

  • Prof. Andrew Wilson (University of Leeds)
15 september 2016
Science Campus
Einsteinweg 55
2333 CC Leiden

The chemical biology lecture committee is pleased to announce Prof. Andrew Wilson from the University of Leeds as the first lecturer of the new year. Prof. Wilson has focused his research on tackling one of the most difficult biomolecular interactions, namely the large surface protein-protein interactions. By using a combination of crystallographic studies, design and synthesis he has created some very elegant ‘proteomimetics’, which can mimic the interacting surface of a protein and has used these to unravel protein-protein interaction biochemistry.


Figure 1. Fundamental Studies in the Wilson Group (a) aromatic oligoamides as α-helix mimetics (b) ruthenium (II) tris-bipyridyl protein surface mimetics

Protein-protein interactions (PPIs) play a pivotal role in diseased states; what is not clear is how to do modulate PPIs using a small molecule, given that it must cover 800-1100Å2 of a protein surface and complement the discontinuous projection of hydrophobic and charged domains over a flat or moderately convex surface. Several general approaches tailored to particular protein topologies are emerging for the design of scaffolds that inhibit PPIs including: ‘proteomimetics’ and ‘surface mimetics’.[1-2] This presentation will describe our work on proteomimetics (Fig. 1a) which replicate the spatial projection of key binding residues from a secondary structural motif[1] important in the target protein-protein interaction and surface mimetics (Fig. 1b) which present recognition domains from a core scaffold in a multivalent manner to achieve high affinity protein recognition.[2]


 [1] (a) G. M. Burslem, H. F. Kyle, A. L. Breeze, T. A. Edwards, A. S. Nelson, S. L. Warriner, A. J. Wilson, Chem. Commun., 2016, 52, 5421-5424 (b) J. A. Miles, D. J. Yeo, Philip Rowell, S. Rodriguez-Marin, C. M. Pask, S. L. Warriner, T. A. Edwards, A. J. Wilson, Chem. Sci., 2016, 7, 3694-3702, (c) A. Barnard, K. Long, H. L. Martin, J. A. Miles, T. A. Edwards, D. C. Tomlinson, A. Macdonald, A. J. Wilson, Angew. Chem. Int. Ed., 2015, 54, 2960-2965
 [2] (a) A. J. Wilson, J. R. Ault, M. H. Filby H. I. A. Philips, A. E. Ashcroft, N, C. Fletcher, Org. Biomol. Chem., 2013, 11, 2206-2212 (b) M. H. Filby, J. Muldoon, S. Dabb, N. C. Fletcher, A. E. Ashcroft, A. J. Wilson, Chem. Commun., 2011, 559-561

Wilson Group