title: Alpha-conotoxin analogs with enhanced affinity for nicotinic receptors and acetylcholine-binding proteins.
abstract: Alpha-conotoxins, neurotoxic peptides from poisonous Conus marine snails, can be subdivided into several groups targeting distinct subtypes of nicotinic acetylcholine receptors (nAChRs). Such alpha-conotoxins as, for example, GI, MI, or SIA potently block muscle-type nAChRs from muscles and from the electric organ of Torpedo ray, whereas others target distinct neuronal nAChRs: alpha-conotoxins ImI and PnIB block pentaoligomeric alpha7 nAChRs, and alpha-conotoxins MII or PnIA inhibit heteromeric nAChRs made of combinations of alpha3 or alpha6 subunits with beta2 subunit. alpha-Conotoxins interact with N-terminal extracellular ligand-binding domains of nAChRs and are indispensable tools for distinguishing various subtypes of AChRs at normal and pathological states. Although many alpha-conotoxins have been isolated from Conus venoms, there is still a great need in more potent and selective tools, which in principle can be obtained by design and synthesis of novel alpha-conotoxin analogs.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. vits@ibch.ru
authors.forename: Victor I
authors.initials: VI
authors.lastname: Tsetlin
authors.forename: Igor E
authors.initials: IE
authors.lastname: Kasheverov
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Zhmak
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Utkin
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Vulfius
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.forename: Daniel
authors.initials: D
authors.lastname: Bertrand
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D020916:Conotoxins / Q000493:pharmacokinetics*; D009474:Neurons / Q000502:physiology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014101:Torpedo
chemical_list: D002352:Carrier Proteins; D020916:Conotoxins; D011978:Receptors, Nicotinic; D000109:Acetylcholine