Conotoxins as research tools and drug leads


Autoria(s): Armishaw, Christopher J.; Alewood, Paul F.
Data(s)

01/06/2005

Resumo

The complex mixture of biologically active peptides that constitute the venom of Conus species provides a rich source of ion channel neurotoxins. These peptides, commonly known as conotoxins, exhibit a high degree of selectivity and potency for different ion channels and their subtypes making them invaluable tools for unravelling the secrets of the nervous system. Furthermore, several conotoxin molecules have profound applications in drug discovery, with some examples currently undergoing clinical trials. Despite their relatively easy access by chemical synthesis, rapid access to libraries of conotoxin analogues for use in structure-activity relationship studies still poses a significant limitation. This is exacerbated in conotoxins containing multiple disulfide bonds, which often require synthetic strategies utilising several steps. This review will examine the structure and activity of some of the known classes of conotoxins and will highlight their potential as neuropharmacological tools and as drug leads. Some of the classical and more recent approaches to the chemical synthesis of conotoxins, particularly with respect to the controlled formation of disulfide bonds will be discussed in detail. Finally, some examples of structure-activity relationship studies will be discussed, as well as some novel approaches for designing conotoxin analogues.

Identificador

http://espace.library.uq.edu.au/view/UQ:75905

Idioma(s)

eng

Publicador

Bentham Science Publ Ltd

Palavras-Chave #Conotoxins #Solid-phase Peptide Synthesis #Protecting Groups #Disulfide Bonds #Structure-activity Relationship Studies #Biochemistry & Molecular Biology #Nicotinic Acetylcholine-receptor #Sensitive Calcium-channel #Conus-geographus Venom #Muscle Sodium-channels #Solid-phase Synthesis #Single Amino-acid #Acetamidomethyl-cysteine-peptides #3-dimensional Solution Structure #Gamma-carboxyglutamic Acid #Nuclear-magnetic-resonance #C1 #250302 Biological and Medical Chemistry #780103 Chemical sciences
Tipo

Journal Article