Coordinatore | ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Organization address
address: BATIMENT CE 3316 STATION 1 contact info |
Nazionalità Coordinatore | Switzerland [CH] |
Totale costo | 199˙317 € |
EC contributo | 199˙317 € |
Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
Code Call | FP7-PEOPLE-2013-IEF |
Funding Scheme | MC-IEF |
Anno di inizio | 2014 |
Periodo (anno-mese-giorno) | 2014-06-01 - 2016-05-31 |
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1 |
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Organization address
address: BATIMENT CE 3316 STATION 1 contact info |
CH (LAUSANNE) | coordinator | 199˙317.60 |
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'Peptide macrocycles can bind with high affinity and selectivity to protein targets and are an attractive class of molecules for the development of therapeutics. Recently, a phage display-based strategy was developed that allowed to generate potent bicyclic peptide antagonists (Heinis, C., et al., Nat. Chem. Biol., 2009). While bicyclic peptides with nanomolar affinities to a range of protein targets could be generated, it was more difficult to obtain high-affinity binders to some proteins, particularly to those having flat surfaces and no clefts or cavities. Herein, I propose to develop rigid, tricyclic peptides that should, due to a more defined three-dimensional structure, bind to flat surfaces similar as antibodies. Two formats are envisioned for the synthesis of tricyclic peptides: in the first one, a linear peptide is anchored via four cysteine residues to a small molecule while in the second format, bicyclic peptides will be generated and their two peptide rings are connected via Huisgen cycloaddition reaction to impose an additional conformational constraint. Phage-encoded combinatorial libraries of these peptide folds will be generated and subjected to affinity selections. Tricyclic peptide binding to a variety of biological targets including (a) the well-characterized cancer-associated targets EGFR and HER2, and (b) the more challenging target of the antibiotic vancomycin, the short peptide D-Ala-D-Ala, will be developed.'
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