Abstract
Nicotinic acetylcholine receptors (nAChRs) are pentameric membrane-bound proteins belonging to the large family of ligandgated ion channels. nAChRs possess various binding sites which interact with compounds of different chemical nature, including peptides. Historically first peptides found to act on nAChR were synthetic fragments of snake α-neurotoxins, competitive receptor antagonists. Later it was shown that fragments of glycoprotein from rabies virus, having homology to α-neurotoxins, and polypeptide neurotoxins waglerins from the venom of Waglers pit viper Trimeresurus (Tropidolaemus) wagleri bind in a similar way, waglerins being efficient blockers of muscle-type nAChRs. Neuropeptide substance P appears to interact with the channel moiety of nAChR. β-Amyloid, a peptide forming senile plaques in Alzheimers disease, also can bind to nAChR, although the mode of binding is still unclear. However, the most well-studied peptides interacting with the ligand-binding sites of nAChRs are so-called α-conotoxins, peptide neurotoxins from marine snails of Conus genus. First α-conotoxins were discovered in the late 1970s, and now it is a rapidly growing family due to isolation of peptides from multiple Conus species, as well as to cloning, and chemical synthesis of new analogues. Because of their unique selectivity towards distinct nAChR subtypes, α-conotoxins became valuable tools in nAChR research. Recent X-ray structures of α- conotoxin complexes with acetylcholine-binding protein, a model of nAChR ligand-binding domains, revealed the details of the nAChR ligand-binding sites and provided the basis for design of novel ligands.
Keywords: Nicotinic acetylcholine receptor, peptides, α-conotoxins
Current Pharmaceutical Design
Title: Naturally Occurring and Synthetic Peptides Acting on Nicotinic Acetylcholine Receptors
Volume: 15 Issue: 21
Author(s): Igor E. Kasheverov, Yuri N. Utkin and Victor I. Tsetlin
Affiliation:
Keywords: Nicotinic acetylcholine receptor, peptides, α-conotoxins
Abstract: Nicotinic acetylcholine receptors (nAChRs) are pentameric membrane-bound proteins belonging to the large family of ligandgated ion channels. nAChRs possess various binding sites which interact with compounds of different chemical nature, including peptides. Historically first peptides found to act on nAChR were synthetic fragments of snake α-neurotoxins, competitive receptor antagonists. Later it was shown that fragments of glycoprotein from rabies virus, having homology to α-neurotoxins, and polypeptide neurotoxins waglerins from the venom of Waglers pit viper Trimeresurus (Tropidolaemus) wagleri bind in a similar way, waglerins being efficient blockers of muscle-type nAChRs. Neuropeptide substance P appears to interact with the channel moiety of nAChR. β-Amyloid, a peptide forming senile plaques in Alzheimers disease, also can bind to nAChR, although the mode of binding is still unclear. However, the most well-studied peptides interacting with the ligand-binding sites of nAChRs are so-called α-conotoxins, peptide neurotoxins from marine snails of Conus genus. First α-conotoxins were discovered in the late 1970s, and now it is a rapidly growing family due to isolation of peptides from multiple Conus species, as well as to cloning, and chemical synthesis of new analogues. Because of their unique selectivity towards distinct nAChR subtypes, α-conotoxins became valuable tools in nAChR research. Recent X-ray structures of α- conotoxin complexes with acetylcholine-binding protein, a model of nAChR ligand-binding domains, revealed the details of the nAChR ligand-binding sites and provided the basis for design of novel ligands.
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Cite this article as:
Kasheverov E. Igor, Utkin N. Yuri and Tsetlin I. Victor, Naturally Occurring and Synthetic Peptides Acting on Nicotinic Acetylcholine Receptors, Current Pharmaceutical Design 2009; 15 (21) . https://dx.doi.org/10.2174/138161209788682316
DOI https://dx.doi.org/10.2174/138161209788682316 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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