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“Solid phase synthesis, biophysical study and biological evaluation of cyclic glycopeptides for inhibition of protein protein interactions” (Glycopeptides)
Start date: 06 Nov 2008, End date: 05 Nov 2010 PROJECT  FINISHED 

Dr. Jarikote, an Indian national who has recently completed his PhD in Germany and is currently working with Prof. Dr. Paul Murphy. It is proposed that Dr. Jarikote will work on solid phase synthesis of cyclic glycopeptides and their biophysical characterization with a view to generating novel inhibitors of protein-protein interactions, in particular those that involve a-helices. He will also receive training in carbohydrate chemistry, scaffolds, NMR and molecular modelling and their application to the design of bioactive compounds wherever necessary. The biophysical characterisation will also carried out and techniques such as NMR and fluorescence will be used to investigate binding of synthetic ligands to targeted proteins. Such synthetic mimics could have wide pharmaceutical importance as they have potential to be bioavailable mimics of peptides that modulate protein-protein interactions. The proposal is of interdisciplinary nature, collaborating ultimately with physical chemists and cell biologists and will focus on the design, synthesis and biological evaluation of novel proteomimetics or peptidomimetics based on macrocycles comprised of saccharide structures. Mimetics of the surface of the Bak peptide (an alpha-helical peptide) based on glycopeptides will be synthesised on the solid phase and the products will be evaluated for their biophysical properties effects on promoting apoptosis in tumour cells. The solid phase synthesis approach will give rise to rapid access of numerous derivatives of target oriented glycopeptides in short time period. The glycopeptides design will be based on ensuring the presentation of pharmacophoric groups in a spatial orientation that matches that of residues at i, i+4 and i+7 of the relevant α–helical peptide, in this case the BAK peptide. The solid phase approach will faciliate efficient investigation of a number of pharmacophoric groups that will allow generation of an optimal ligand that mimics the natural peptide.
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