Dear Crystallographers... We have an EU funded studentship to study α-Helix Mimetics as Inhibitors of Protein-Protein Interactions Involved in Cancer Development and Progression. Please forward to anybody who may be interested.
The purpose of this project is to develop a RULE-BASED APPROACH for the design and synthesis of inhibitors of key protein-protein interactions (PPIs) involved in the development and progression of cancer. The project is concerned with the analysis of a series of scaffolds designed to act as *-helix mimetics. These scaffolds are amenable to high-throughput solid-phase synthesis and thus the generation of libraries. We have recently shown that these scaffolds can be functionalised such that they inhibit the p53-hDM2 interaction (an oncogenic target) with high (*M affinity). The student will develop cell based assays to test novel aromatic oligoamides as proteomimetic inhibitors of three cancer targets: p53/hDM2, Bcl-xL/BAK and Mcl-1/NOXA-B. The student will also perform detailed biophysical analysis and structural studies including X-ray crystallography, NMR and isothermal titration calorimetry on the inhibitors and their interactions with the target protein. Inhibitors of the hDM2/p53 interaction are being sought to decrease tumour growth, with potential clinical applications in a broad range of cancers, including breast cancer (more than half of human cancers express a mutant p53). Bcl-xL and Mcl-1 are members of the Bcl-2 family of proteins and have also been proposed to be a means of intervention against various cancers including prostate cancer and small cell lung carcinoma. This multidisciplinary project will provide opportunities for the student to receive training in molecular biology, structural biology, molecular modelling and biophysical analysis. For details, and how to apply, please see: http://www.bmb.leeds.ac.uk/staff/tae/ERC_Studentship.pdf Cheers Ed ______________ T.Edwards Ph.D. Garstang 8.53d Astbury Centre for Structural Molecular Biology University of Leeds, Leeds, LS2 9JT Telephone: 0113 343 3031 http://www.bmb.leeds.ac.uk/staff/tae/ Science is always wrong. It never solves a problem without creating ten more. ~George Bernard Shaw
