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Parallel De Novo Design and Screening of multiple site-specific Cell-Permeable β-Hairpin-based Inhibitors

Objective

The primary goal of this project is to integrate advanced techniques for the generation of Permeable β-hairpin-derived Inhibitors (PβhdI) of intracellular targets. Specifically, the approach will combine site recognition and epitope discovery from de novo design with enhanced affinity achieved through phage-display maturation. Additionally, it will improve stability and permeability via interstrand crosslinking (e.g. using bis-electrophiles or disulfides), which will also facilitate phage library diversification. By using these techniques synergistically, the project aims to significantly advance the design of intracellular drugs, potentially broadening the range of available therapeutic options and enhancing the efficacy of targeted treatments. The methodology focuses on the large-scale design and characterization of cell-PβhdI that target multiple binding sites on an intracellular therapeutic target, such as β-catenin. β-Catenin, a key component of the Wnt signaling pathway, is an attractive intracellular target due to its role in various cancers driven by aberrant Wnt signaling. The heterovalent nature of β-catenin, which possesses four distinct binding sites and well-characterized crystal structures, provides an ideal framework for assessing the effectiveness of multiple site-specific binders. Those, combined with the host institution's expertise in studying this oncogene, makes β-catenin an ideal candidate for applying and refining this new methodology.

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.

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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.

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.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

STICHTING VU
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 232 916,16
Address
DE BOELELAAN 1105
1081 HV Amsterdam
Netherlands

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Activity type
Higher or Secondary Education Establishments
Links
Total cost

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.

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