Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IEF
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
1015 Lausanne
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.