TAILIEUCHUNG - Báo cáo khoa học: a-Conotoxin analogs with additional positive charge show increased selectivity towards Torpedo californicaand some neuronal subtypes of nicotinic acetylcholine receptors

a-Conotoxins from Conussnails are indispensable tools for distinguishing various subtypes of nicotinic acetylcholine receptors (nAChRs), and synthe-sis of a-conotoxin analogs may yield novel antagonists of higher potency and selectivity. We incorporated additional positive charges intoa-conotox-ins and analyzed their binding to nAChRs. | ễFEBS Journal a-Conotoxin analogs with additional positive charge show increased selectivity towards Torpedo californica and some neuronal subtypes of nicotinic acetylcholine receptors Igor E. Kasheverov1 Maxim N. Zhmak1 Catherine A. Vulfius2 Elena V. Gorbacheva2 Dmitry Y. Mordvintsev1 Yuri N. Utkin1 Rene van Elk3 August B. Smit3 and Victor I. Tsetlin1 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Moscow Russia 2 Institute of CellBiophysics Russian Academy of Sciences Pushchino Russia 3 Department of Molecular and Cellular Neurobiology Center for Neurogenomics and Cognitive Research Vrije Universiteit Amsterdam the Netherlands Keywords acetylcholine-binding protein acetylcholine-elicited Cl-current a-conotoxin analogs identified Lymnaea neurons nicotinic acetylcholine receptor Correspondence V. I. Tsetlin Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences Miklukho-Maklaya str. 16 10 Moscow Russia Tel Fax 7 495 335 57 33 E-mail vits@ Received 28 March 2006 revised 16 June 2006 accepted 4 August 2006 doi a-Conotoxins from Conus snails are indispensable tools for distinguishing various subtypes of nicotinic acetylcholine receptors nAChRs and synthesis of a-conotoxin analogs may yield novel antagonists of higher potency and selectivity. We incorporated additional positive charges into a-conotox-ins and analyzed their binding to nAChRs. Introduction of Arg or Lys residues instead of Ser12 in a-conotoxins GI and SI or D12K substitution in a-conotoxin SIA increased the affinity for both the high- and low-affinity sites in membrane-bound Torpedo californica nAChR. The effect was most pronounced for D12K SIA with 30- and 200-fold enhancement for the respective sites resulting in the most potent a-conotoxin blocker of the Torpedo nAChR among those tested. Similarly D14K substitution in a-conotoxin A10L PnIA a blocker of neuronal a7 nAChR was previously shown to .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• breast cancer
• medicine
• chemical reaction
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• cell proliferation
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine