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Content archived on 2024-05-27

Cyclic peptides as carbohydrates receptors

Objective

In the last years, considerable effort has been directed to unravel the mechanisms involved in these recognition processes by the design of peptide derived receptors for the selective binding of glycoconjugates. This project will be addressed towards this aim and it will be focused on the development of cyclic peptide receptors for the selective binding of carbohydrates. By using solid-phase combinatorial organic chemistry methodologies, libraries of receptors will be synthesized and screened towards different sugars (e. g. mono- and disaccharides), depending on the cavity shape and size. It is intended to create an efficient tool for the elucidation of the geometric requirements needed for efficient carbohydrate complexatian. Furthermore, due to the enzymatic stability of cyclic peptides as compared to their linear counterparts, these receptors may be interesting targets for drug discovery. The design of these receptors will be based on the stabilizing interaction between the a-face of monosaccharides and aromatic surfaces embedded into a peptide backbone, which may trigger additional interactions between the carbohydrate and the peptide (mostly hydrogen bonds). The modification of the receptor elements in a combinatorial fashion may lead to identification of tight complexes ( e. g. fluorescence assays, BIAcore) which structure will be analyzed (e. g. MALDI- TOF, NMR, Edman degradation, molecular modeling) to obtain the complete interaction pattern between sugar hydroxyl groups and peptide amido groups. Structure/binding efficiency relationship will also be determined towards the development of saccharide bio-sensors, drug or selective carbohydrate transport systems. This project offers the candidate the possibility to improve his knowledge in solid-phase organic chemistry methodologies, not only in the peptide field not so in others, including carbohydrates. Furthermore, it will give the candidate an essential formation in combinatorial chemistry and library screening techniques (e. g. on-bead fluorescence assays to detect lead compounds, NMR for structure characterization, or surface plasmon resonance to disclose the thermodynamic parameters of complexation). The acquired knowledge will be very useful for the candidate in the development of his further projects linked to the understanding of the interaction between proteins and carbohydrate, which play an elemental role in biological processes and may lead to biomedical applications.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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Funding Scheme

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RGI - Research grants (individual fellowships)

Coordinator

CARLSBERG LABORATORY
EU contribution
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Address
10,Gamle Carlsberg Vej 10
2500 VALBY
Denmark

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Total cost

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