tailieunhanh - Báo cáo khoa học: Physico-chemical characterization and synthesis of neuronally active a-conotoxins

The high specificity ofa-conotoxins for different neuronal nicotinic acetylcholine receptors makes them important probes for dissecting receptor subtype selectivity. New sequences continue to expand the diversity and utility of the pool of available a-conotoxins. Their identification andcharacterizationdependonasuiteoftechniques with increasing emphasis on mass spectrometry and micro-scale chromatography, which have benefited from recent advances in resolution and capability. Rigorous physico-chemical analysis together with synthetic peptide chemistry is a prerequisite for detailed conformational analysis and to provide sufficient quantities ofa-conotoxins for activity assessment and structure–activity relationship studies | Eur. J. Biochem. 271 2294-2304 2004 FEBS 2004 doi MINIREVIEW Physico-chemical characterization and synthesis of neuronally active a-conotoxins Marion L. Loughnan and Paul F. Alewood Institute for Molecular Bioscience The University of Queensland Brisbane Australia The high specificity of a-conotoxins for different neuronal nicotinic acetylcholine receptors makes them important probes for dissecting receptor subtype selectivity. New sequences continue to expand the diversity and utility of the pool of available a-conotoxins. Their identification and characterization depend on a suite of techniques with increasing emphasis on mass spectrometry and microscale chromatography which have benefited from recent advances in resolution and capability. Rigorous physicochemical analysis together with synthetic peptide chemistry is a prerequisite for detailed conformational analysis and to provide sufficient quantities of a-conotoxins for activity assessment and structure-activity relationship studies. Keywords a-conotoxins Conus peptide synthesis post-translational modifications sulfotyrosine. Classification primary structure and biology of a-conotoxins Cone snails are a group of hunting gastropods that incapacitate their prey which consists of worms molluscs or fish by envenomation. Conotoxins from the venom of cone snails are small disulfide-rich peptide toxins that act at many voltage-gated and ligand-gated ion channels. They can be grouped according to their molecular form into several superfamilies each defined by characteristic arrangements of cysteine residues not necessarily a single pattern and characteristic highly conserved precursor signal sequence similarities. Individual conopeptide families within a superfamily are denoted by Greek letters and contain peptides that have a particular disulfide framework and target homologous sites on a particular receptor 1 . Each of the characterized conopeptides is named using a convention that