Structure-activity studies on alpha-conotoxins.
Conotoxins are small bioactive highly structured peptides from the venom of marine cone snails (genus Conus). Over the past 50 million years these molluscs have developed a complex venom cocktail for each species that is comprised of 100-2000 distinct cysteine- rich peptides for prey capture and defence. This review focuses on an important and well-studied class of conotoxins, the α- conotoxins. These α-conotoxins are potent and selective antagonists of various subtypes of the nicotinic acetylcholine receptors (nAChRs). Key structure-activity relationship studies are presented to illustrate the common motifs, structural features and pharmacophores that define this interesting peptide class. Additionally, their synthesis, chemical modifications, the development of more selective and stable analogues and their therapeutic potential are discussed.
Institute for Molecular Bioscience, The University of Queensland, St Lucia Queensland 4072, Australia.
Markus
M
Muttenthaler
Kalyana B
KB
Akondi
Paul F
PF
Alewood
D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D052078:Conus Snail / Q000737:chemistry; D055808:Drug Discovery; D006801:Humans; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry; D018733:Nicotinic Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011978:Receptors, Nicotinic / Q000378:metabolism; D013329:Structure-Activity Relationship
D020916:Conotoxins; D008978:Mollusk Venoms; D018733:Nicotinic Antagonists; D010456:Peptides, Cyclic; D011978:Receptors, Nicotinic