{"id":4870,"date":"2023-02-17T07:06:14","date_gmt":"2023-02-17T07:06:14","guid":{"rendered":"http:\/\/ionchanneltargets.com\/resource_library\/nav1-5-high-throughput-pharmacology-of-nav1-5-channels-on-nanions-syncropatch-384pe\/"},"modified":"2023-02-17T07:06:15","modified_gmt":"2023-02-17T07:06:15","slug":"2012-design-synthesis-and-functional-analysis-of-dansylated-polytheonamide-mimic-an-artificial-peptide-ion-channel","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2012-design-synthesis-and-functional-analysis-of-dansylated-polytheonamide-mimic-an-artificial-peptide-ion-channel\/","title":{"rendered":"2012 &#8211; Design, synthesis and functional analysis of dansylated polytheonamide mimic: an artificial Peptide ion channel"},"content":{"rendered":"<p>We report herein the design, total synthesis, and functional analysis of a novel artificial ion channel molecule, designated as dansylated polytheonamide mimic (3). The channel\u00a03\u00a0was designed based on an exceptionally potent cytotoxin, polytheonamide B (1). Our strategy for the development of synthetic ion channels, which could be easily derivatized for various functions, involved two key features. First, the structure of\u00a01\u00a0was simplified by replacing many of nonproteinogenic amino acid residues which required multistep synthesis by commercially available amino acids while retaining those residues necessary for folding. It significantly reduced the number of synthetic steps and facilitated a practical chemical construction of\u00a03. Second, the introduction of propargyl glycine at residue 44 enabled facile installation of dansyl group as a reporter of the membrane localization of\u00a03. Application of a newly designed protective group strategy provided efficient construction of the 37 amino acid sequence of residues 12\u201348 through one automatic solid-phase peptide synthesis. After peptide cleavage from the resin,\u00a03\u00a0was synthesized via dansyl group introduction and one fragment-coupling reaction with residues 1\u201311, followed by the global deprotection. The simplified mimic\u00a03\u00a0exhibited potent cytotoxicity toward p388 mouse leukemia cells (IC<sub>50<\/sub>\u00a0= 12 nM), effectively induced ion transport across the lipid bilayers of liposomes, and displayed H+\u00a0and Na<sup>+<\/sup>\u00a0ion channel activities. Because of its simplified yet functional scaffold structure with a potential for diversification, our rationally designed ion channel molecule should be useful as a novel platform for developing various cytotoxic channel molecules with additional desired functions.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45,129],"resource_type":[75],"application_areas":[50,53],"therapeutic_areas":[],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-4870","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","products_tags-vesicle-prep-pro","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/4870","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=4870"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=4870"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=4870"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=4870"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=4870"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=4870"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=4870"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=4870"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=4870"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}