Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

FP6

DSCC Sintesi della relazione

Project ID: 40451
Finanziato nell'ambito di: FP6-MOBILITY
Paese: Sweden

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.

Reported by

GOTEBORG UNIVERSITY
40530 GOTEBORG
Sweden