DSCC · Design, synthesis and characterisation of Conotoxins
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2006-11-01 → 2008-10-31
- EU contribution
- €167,056
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - DSCC (Design, Synthesis and Characterisation of Conotoxins)
This project aimed at the development of novel strategies for the design, synthesis and characterisation of conotoxins. Conotoxins form a large family of peptide toxins from cone snail venoms that act on a broad spectrum of ion channels and receptors. The subgroup a-conotoxins specifically and selectively bind to subtypes of nicotinic acetylcholine receptors (8nAchRs), which are targets for treatment of several neurological disorders. The project has generated a range of interesting results that include: a) Development of solid-phase microwave assisted synthesis of peptides in water. We have developed a highly efficient, environmentally friendly strategy for solid-phase peptide synthesis in water. b) Development of protocols for on-bead preparation of disulfide bridges. We have developed and evaluated different strategies for how to generate the disulfide bridges in a-conotoxin MII in the most efficient way. A combination of on-bead and solution phase gave the highest yields and best purity. c) Developments of strategies for the replacing the disulfide bridges with isosters. Two different strategies were attempted (based on Ru-catalysed metathesis and Cu catalysed 1,3 cycloaddition). The efficiency depends both on how many amino acids and the nature of the amino acids that are placed between the two residues reacting with each other. These results are important contributions to the development of general synthetic strategies for the preparation of conotoxins and derivatives. Such strategies are essential to efficiently approach important questions within the area of neurobiology and for the development of novel drugs for treatment of various neurological diseases.
Data: CORDIS, © European Union
Project objective
This project aims at the development of novel strategies for the Design, Synthesis and Characterisation of Conotoxins (DSCC). Conotoxins form a large family of peptide toxins from cone snail venoms that act on a broad spectrum of ion channels and receptors.The subgroup a-conotoxins specifically and selectively bind to subtypes of nicotinic acetylcholine receptors 8nAchRs), which are targets for treatment of several neurological disorders.The development of synthetic strategies for conotoxins and derivatives are essential to efficiently approach important questions within the area of neurobiology and to meet the need for novel drugs with new mechanisms of action useful in treatments for important diseases such as chronic pain and Parkinson disease.The EIF will receive advanced training in the S and T competences necessary to perform high-level research and to generate new knowledge on synthesis of conotoxins. The EIF will carry out his project in an exciting, active and dynamic research environment.His project will focus on achieving the following ambitious scientific objectives:- Development of new synthetic strategies for generation of conotoxin and derivatives- Development of state-of-the-art methods for design, synthesis, characterisation and application of such compounds- To examine fundamental aspects of the design and synthesis of conotoxin derivatives in order to provide a greater understanding of what parameters govern the biological function of the compounds.The main training objectives of this research-training project are:- Providing advanced training tailored the EIF to needs with a view to adding different/complementary scientific competencies in organic chemistry, structural biology and pharmacology- To enhance both the EIF research capacities and complementary skills to enable him to establish an independent research career
Original text from CORDIS.
Participants
- GÖTEBORG UNIVERSITY · GÖTEBORGCoordinatorCity levelSweden
Links
Data: CORDIS, © European Union