Objective
"Background and problem: Many disease targets, including a wide range of intracellular protein–protein interactions (PPIs), exhibit flat, featureless surfaces. This means that it is very difficult to develop small-molecule ligands against these targets and to modulate them therapeutically. Ultimately, thus, many major diseases for which therapeutic targets are known remain untreated. Small, non-polar cyclic peptides have aroused much excitement as an answer to this problem due to their ability to cross membranes and bind challenging targets. However, there are currently no methods for generating and screening sufficiently large and diverse libraries of membrane-permeable cyclic peptides.
Objectives and strategy/ideas: My goal is to drastically push the boundaries of library size and diversity. I will achieve this by generating pools of small, membrane-permeable cyclic peptides that are unprecedently large (> 100 million) and chemically diverse (> 1,000 different chemical building blocks) and will screen these peptides against challenging targets. I will employ DNA tagging to encode the libraries, a strategy that has proven highly effective for small molecules but not for peptide libraries due to technical challenges in synthesising molecules with so many building blocks. To address these barriers and enable the creation of DNA-encoded cyclic peptide libraries, I propose four novel strategies that I will apply to develop binders for important disease targets that have proven particularly challenging to drug, including STAT3, NF-κB, MYC, β-catenin, and IL-23R.
Outcome and impact: I anticipate that these new methods will yield membrane-permeable ligands for several of the named targets, providing urgently needed starting points for drug development. Most importantly, I expect to establish a powerful method that will be broadly applied in academia and industry. to a wide range of diseases currently tagged as ""undruggable,"" ultimately benefiting large numbers of patients."
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 genetics DNA
- natural sciences biological sciences biochemistry biomolecules
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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)
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.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
HORIZON-ERC - HORIZON ERC Grants
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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.
(opens in new window) ERC-2025-ADG
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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.
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.