title: Chemical synthesis and characterization of two α4/7-conotoxins.
abstract: α-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors (nAChRs). We previously cloned two α-conotoxins, Mr1.1 from the molluscivorous Conus marmoreus and Lp1.4 from the vermivorous Conus leopardus. Both of them have the typical 4/7-type framework of the subfamily of α-conotoxins that act on neuronal nAChRs. In this work, we chemically synthesized these two toxins and characterized their functional properties. The synthetic Mr1.1 could primarily inhibit acetylcholine (ACh)-evoked currents reversibly in the oocyte-expressed rat α7 nAChR, whereas Lp1.4 was an unexpected specific blocker of the mouse fetal muscle α1β1γδ receptor. Although their inhibition affinities were relatively low, their unique receptor recognition profiles make them valuable tools for toxin-receptor interaction studies. Mr1.1 could also suppress the inflammatory response to pain in vivo, suggesting that it should be further investigated with respect to its molecular role in analgesia and its mechanism or therapeutic target for the treatment of pain.
authors.affiliation: Institute of Protein Research, Tongji University, Shanghai, China.
authors.forename: Can
authors.initials: C
authors.lastname: Peng
authors.forename: Weihua
authors.initials: W
authors.lastname: Chen
authors.forename: Tanya
authors.initials: T
authors.lastname: Sanders
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Chew
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Edward
authors.initials: E
authors.lastname: Hawrot
authors.forename: Chengwu
authors.initials: C
authors.lastname: Chi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology; D002351:Carrageenan; D018679:Cholinergic Agonists / Q000494:pharmacology; D020916:Conotoxins / Q000138:chemical synthesis* / Q000235:genetics / Q000494:pharmacology*; D052078:Conus Snail / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000517:prevention & control; D008297:Male; D013058:Mass Spectrometry; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D000700:Analgesics; D002121:Calcium Channel Blockers; D018679:Cholinergic Agonists; D020916:Conotoxins; D011978:Receptors, Nicotinic; D002351:Carrageenan; D000109:Acetylcholine
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