{"id":4890,"date":"2023-02-17T07:02:06","date_gmt":"2023-02-17T07:02:06","guid":{"rendered":"http:\/\/ionchanneltargets.com\/resource_library\/qualification-of-patch-ready-cells-on-a-syncropatch-384pe\/"},"modified":"2023-02-17T07:02:06","modified_gmt":"2023-02-17T07:02:06","slug":"2012-isolation-characterization-and-total-regioselective-synthesis-of-the-novel-%ce%bco-conotoxin-mfvia-from-conus-magnificus-that-targets-voltage-gated-sodium-channels","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2012-isolation-characterization-and-total-regioselective-synthesis-of-the-novel-%ce%bco-conotoxin-mfvia-from-conus-magnificus-that-targets-voltage-gated-sodium-channels\/","title":{"rendered":"2012 &#8211; Isolation, characterization and total regioselective synthesis of the novel \u03bcO-conotoxin MfVIA from Conus magnificus that targets voltage-gated sodium channels"},"content":{"rendered":"<p>The \u03bcO-conotoxins are notable for their unique selectivity for NaV1.8 over other sodium channel isoforms, making them attractive drug leads for the treatment of neuropathic pain. We describe the discovery of a novel \u03bcO-conotoxin, MfVIA, from the venom of\u00a0Conus magnificus\u00a0using high-throughput screening approaches. MfVIA was found to be a hydrophobic 32-residue peptide (amino acid sequence RDCQEKWEYCIVPILGFVYCCPGLICGPFVCV) with highest sequence homology to \u03bcO-conotoxin MrVIB. To overcome the synthetic challenges posed by \u03bcO-conotoxins due to their hydrophobic nature and difficult folding, we developed a novel regioselective approach for the synthesis of \u03bcO-conotoxins. Performing selective oxidative deprotections of the cysteine side-chain protecting groups of the fully protected peptide allowed manipulations in organic solvents with no chromatography required between steps. Using this approach, we obtained correctly folded MfVIA with increased synthetic yields. Biological activity of MfVIA was assessed using membrane potential-sensitive dyes and electrophysiological recording techniques. MfVIA preferentially inhibits NaV1.8 (IC<sub>50<\/sub>\u00a095.9\u00a0\u00b1\u00a074.3\u00a0nM) and NaV1.4 (IC<sub>50<\/sub>\u00a081\u00a0\u00b1\u00a016\u00a0nM), with significantly lower affinity for other NaV\u00a0subtypes (IC<sub>50<\/sub>\u00a0431\u20136203\u00a0nM; NaV1.5\u00a0>\u00a01.6\u00a0\u223c\u00a01.7\u00a0\u223c\u00a01.3\u00a0\u223c\u00a01.1\u00a0\u223c\u00a01.2). This improved approach to \u03bcO-conotoxin synthesis will facilitate the optimization of \u03bcO-conotoxins as novel analgesic molecules to improve pain management.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[56],"target_categories":[61],"target_families":[332],"targets":[93,116,117,212,234,236,244],"resource_keyword":[],"class_list":["post-4890","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-ion-channels","therapeutic_areas-pain","target_categories-voltage-gated-ion-channels","target_families-nav-channels","targets-nav1-5","targets-nav1-7","targets-nav1-8","targets-nav1-2","targets-nav1-1","targets-nav1-3","targets-nav1-6"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/4890","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=4890"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=4890"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=4890"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=4890"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=4890"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=4890"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=4890"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=4890"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=4890"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}