Objective
The area of influence of proteins comprise most biochemical reactions and recognition process that govern a living body. However, its malfunction often lead to devastating diseases, like the ones related to Transthyretin:famylial amyloid polyneuropathy (FAP), famylial amyloid cardiomyopathy (FAC) and systemic senyl amyloidosis (SSA), cureless to date. Chemical approaches to some of these biomacromolecules have been possible after the discovery of the native chemical ligation, which involves assembly of unprotected Cys-peptide and peptidyl-thioester fragments in aqueous environments. Nonetheless, this technique still encompasses major limitations that has prevented its application to virtually all proteins, such as the requirement of N-terminal Cys peptides and low yield in bulky ligation sites. To increase the scope of ligation, thiol-containing building blocks and thiol-directing ligation auxiliaries have been designed, which allow ligation at non-cysteine ligation sites, but are either sequence dependent or lack sufficient efficiency.
In this proposal, we aim to introduce new families of ligation auxiliaries that overcome the classical restrictions of this technique and improve previous strategies. In more detail, two complementary templates will be investigated: mercapto-cyclopentadienil and mercapto-cyclopropylethyl. The former structure is specifically designed to enhance the ligation rate by placing the thiol group in an ideal position with respect to the nitrogen, whereas the latter decreases the sterical hindrance and enhances the acid lability of the auxiliary. To practically illustrate the applicability of this new methodology, the native sequence and mutated analogues of Transthyretin at critical positions will be chemically achieved, a major milestone in the study of this protein, thereby helping understand the biochemical mechanisms that produce the derived pathologies, which cause the death of several thousand people in the world, specially in Europe.
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 biochemistry biomolecules proteins
- medical and health sciences basic medicine pathology
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Programme(s)
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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-2011-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
10117 Berlin
Germany
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.