synthetic α-conotoxin mutants as probes for studying nicotinic acetylcholine receptors and in the development of novel drug leads合成α-conotoxin突变体作为研究尼古丁乙酰胆碱受体的探测和开发新药物先导物.pdfVIP

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synthetic α-conotoxin mutants as probes for studying nicotinic acetylcholine receptors and in the development of novel drug leads合成α-conotoxin突变体作为研究尼古丁乙酰胆碱受体的探测和开发新药物先导物.pdf

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synthetic α-conotoxin mutants as probes for studying nicotinic acetylcholine receptors and in the development of novel drug leads合成α-conotoxin突变体作为研究尼古丁乙酰胆碱受体的探测和开发新药物先导物

Toxins 2010, 2, 147 1-1499; doi:10.3390/toxins2061471 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Synthetic -Conotoxin Mutants as Probes for Studying Nicotinic Acetylcholine Receptors and in the Development of Novel Drug Leads Christopher J. Armishaw Torrey Pines Institute for Molecular Studies, 11350 SW Village Pkwy, Port St Lucie, FL 34987, USA; E-Mail: carmishaw@; Tel.: +1-772-345-4720; Fax: +1-772-345-3649 Received: 1 April 2010; in revised form: 27 May 2010 / Accepted: 11 June 2010/ Published: 14 June 2010 Abstract: α-Conotoxins are peptide neurotoxins isolated from venomous marine cone snails that are potent and selective antagonists for different subtypes of nicotinic acetylcholine receptors (nAChRs). As such, they are valuable probes for dissecting the role that nAChRs play in nervous system function. In recent years, extensive insight into the binding mechanisms of α-conotoxins with nAChRs at the molecular level has aided in the design of synthetic analogs with improved pharmacological properties. This review examines the structure-activity relationship studies involving α-conotoxins as research tools for studying nAChRs in the central and peripheral nervous systems and their use towards the development of novel therapeutics. Keywords: α-conotoxin; nicotinic acetylcholine receptor; acetylcholine binding protein; structure-activity relationship studies; mutational analysis Abb