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Chemical evolution of phosphate receptors. application in kinase substrate recognition

Ziel

Reversible protein phosphorylation is a universal means of regulating many cellular processes. Identification of phosphorylation patterns through selective recognition events would contribute to a better understanding of cellular processes. There is a urgent need for more selective and tailored phosphate receptors. In last years, "directed evolution" approaches have been applied successfully to the synthesis of artificial receptors. The current project aims to develop of a novel methodology for the synthesis of phosphate receptors (and potentially anion receptors in general) and their evolution as receptors for the identification of biologically important kinase substrates. A reversible chemical reaction is used to allow the receptor fragments to join together in the presence of the template (a molecular entity) to form a library of synthetic receptor molecules. The result of which fragments resulted in the highest affinity receptors is the feedback used to optimize the selection of fragments employed in the synthesis of a second-generation library of receptors. The selection process will be terminated when a particular receptor molecule is significantly more abundant than any other or when the receptor fragment composition has remained unchanged in a subsequent library evaluation. The receptors produced in this proposal could become "day-to-day" reagents for biomedical research. The applicant will be able to obtain experience in a new field of research, i.e. synthesis of phosphate receptors and their application in kinase substrate recognition that fit very well to the previously obtained experience. Moreover, he will become familiar with a variety of new characterization and techniques, NMR, FT-IR, UV-Vis, GC/MS, FAB..The interest for the group to host the candidate can be found it:
* The build up of strategic knowledge, to be laid down in publications and patent applications
* Establishing and strengthening contacts with researchers from Spain, thus constructing a European Network
.* Strengthening the group's position in the areas synthetic chemical and chemical biology.
* Knowledge in heterogeneous catalysis.
* Experience in photochemical asymmetric synthesis.

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IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
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