Discussion
Inhibition of ER/Co-activator interaction using α-helix proteomimetics
Silvia Rodriguez Marin, Andrew J. Wilson
Protein-protein interactions play an important role in many biological processes. Therefore, targeting and modulating PPI’s is fundamental in understanding and manipulating mechanisms that govern many diseases. However, proteins display a large diversity of topologies composed of unique exterior surfaces with charged, hydrophobic and hydrophilic domains, which make them difficult to be target with traditional small molecules.[1]
The Estrogen receptor (ER) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. In particular, estrogenic signalling processes are crucial in the development of breast cancer. ER mediates its transcriptional activity through protein-protein interactions with co-activator proteins.[2] Consequently, the ER is an attractive target for development of PPI inhibitors.[3-4]
This poster describes the design and synthesis of novel α-helix proteomimetics[5] that will be used to target the ER/co-activator interaction. Conformational analysis on these dimeric benzamides which reproduce two faces of an -helix will also be described.
References
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[4] C. Phillips, L. R. Roberts, M. Schade, R. Bazin, A. Bent, N. L. Davies, R. Moore, A. D. Pannifer, A. R. Pickford, S. H. Prior, C. M. Read, A. Scott, D. G. Brown, B. Xu, S. L. Irving, J. Am. Chem. Soc. 2011, 133, 9696-9699.
[5] V. Azzarito, P. Prabhakaran, A. I. Bartlett, N. S. Murphy, M. J. Hardie, C. A. Kilner, T. A. Edwards, S. L. Warriner, A. J. Wilson, Org. Biomol. Chem. 2012, 10, 6469-6472.
