Alpha-conotoxin analogs with enhanced affinity for nicotinic receptors and acetylcholine-binding proteins.
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.
Tsetlin
Victor I
VI
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia. vits@ibch.ru
Kasheverov
Igor E
IE
Zhmak
Maxim N
MN
Utkin
Yuri N
YN
Vulfius
Catherine A
CA
Smit
August B
AB
Bertrand
Daniel
D
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
D002352:Carrier Proteins; D020916:Conotoxins; D011978:Receptors, Nicotinic; D000109:Acetylcholine