{"id":17701,"date":"2018-01-19T06:18:25","date_gmt":"2018-01-18T22:18:25","guid":{"rendered":"\/\/www.gsbet888.com\/?p=17701"},"modified":"2019-08-02T18:52:03","modified_gmt":"2019-08-02T10:52:03","slug":"native-chemical-ligation-ncl","status":"publish","type":"post","link":"\/\/www.gsbet888.com\/reactions\/2018\/01\/native-chemical-ligation-ncl.html","title":{"rendered":"Native Chemical Ligation (NCL)"},"content":{"rendered":"<h4>\u6982\u8981<\/h4>\n<p>\u5728\u73b0\u6709\u7684\u80bd\u5408\u6210\u4e2d\uff0c\u968f\u7740\u5206\u5b50\u91cf\u7684\u589e\u52a0\uff0c\u5b98\u80fd\u56e2\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u5448\u6307\u6570\u589e\u957f\uff0c\u5e76\u4e14\u5f53\u53cd\u5e94\u70b9&#8221;\u6f5c\u5165&#8221;\u591a\u80bd\u7ed3\u6784\u5185\u90e8\uff0c\u8fd9\u6837\u5c31\u4f7f\u5f97\u540e\u7eed\u4fee\u9970\u53cd\u5e94\u66f4\u96be\u4ee5\u8fdb\u884c\u3002\u6bd4\u5982\u8bf4\uff0c\u540e\u7eed\u5982\u679c\u8981\u8fdb\u884c\u7f29\u5408\u53cd\u5e94\u4fee\u9970\u7684\u8bdd\uff0c\u53cd\u5e94\u6d3b\u6027\u4f1a\u5927\u5927\u964d\u4f4e\uff0c\u901a\u5e38\u6db2\u76f8\u53cd\u5e94\u6700\u5927\u4e5f\u53ea\u80fd\u8fde10\u4e2a\u6b8b\u57fa\uff0c\u5373\u4f7f\u662f\u56fa\u76f8\u5408\u6210\u6700\u5927\u4e5f\u5c3150\u4e2a\u6b8b\u57fa\uff0c\u5c31\u5df2\u7ecf\u5230\u4e86\u6781\u9650\u4e86\u3002<\/p>\n<p><strong>Native Chemical Ligation(NCL)\u6cd5<\/strong>\u53ef\u4ee5\u6709\u6548\u514b\u670d\u8fd9\u79cd\u969c\u788d\u00a0\u3002<\/p>\n<p>\u5c06\u5728C-\u672b\u7aef\u5177\u6709\u786b\u916f\u7684\u80bd\u548c\u5728N-\u672b\u7aef\u5177\u6709\u672a\u4fdd\u62a4\u7684\u534a\u80f1\u6c28\u9178\u7684\u80bd\uff0c\u5728\u751f\u7269\u76f8\u5bb9\u6027\u6761\u4ef6\u4e0b(pH 7\u300120\u2103\uff5e37\u2103)\u6df7\u5408\u5c31\u53ef\u4ee5\u8fdb\u884c\u53cd\u5e94\uff0c\u5e76\u4e0d\u9700\u8981\u52a0\u5165\u591a\u4f59\u7684\u6d3b\u5316\u8bd5\u5242\u3002\u5bf9\u4e8e\u4fa7\u94fe\u65e0\u4fdd\u62a4\u7684\u591a\u80bd\u4e5f\u80fd\u9ad8\u6548\u53cd\u5e94\u5f97\u5230\u5f88\u597d\u7684\u4ea7\u7387\u3002\u8be5\u53cd\u5e94\u5229\u7528\u591a\u80bd\u4e2d\u672c\u8eab\u5c31\u5177\u6709\u7684\u5b98\u80fd\u56e2(Native Functional Group)\uff0c\u8fd9\u4e00\u70b9\u662f\u975e\u5e38\u6709\u4ef7\u503c\u7684\u3002\u901a\u8fc7\u8fd9\u79cd\u65b9\u6cd5\uff0c\u53ef\u4ee5\u5316\u5b66\u5408\u6210\u9ad8\u8fbe\u7ea6200\u4e2a\u6b8b\u57fa\u7684\u80bd\u94fe\u3002<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-17755 \" src=\"https:\/\/assets.www.gsbet888.com\/uploads\/2018\/01\/2-8-2-A_NCL.png\" alt=\"\" width=\"449\" height=\"347\" srcset=\"https:\/\/assets.www.gsbet888.com\/uploads\/2018\/01\/2-8-2-A_NCL.png 645w, https:\/\/assets.www.gsbet888.com\/uploads\/2018\/01\/2-8-2-A_NCL-300x232.png 300w\" sizes=\"(max-width: 449px) 100vw, 449px\" \/><\/p>\n<p>&nbsp;<\/p>\n<h4>\u57fa\u672c\u6587\u732e<\/h4>\n<ul>\n<li>Dawson, P. E.; Muir, T. W.; Clark-Lewis, I.; Kent, S. B. H. <em>Science<\/em><strong> 1994<\/strong>, <em>266<\/em>, 776. DOI:<a href=\"http:\/\/dx.doi.org\/10.1126\/science.7973629\">10.1126\/science.7973629<\/a><\/li>\n<li>Johnson, E. C. B.; Kent, S. B. H. <em>J. Am. Chem. Soc.<\/em> <strong>2006<\/strong>, <em>128<\/em>, 6640. DOI: <a href=\"http:\/\/dx.doi.org\/10.1021\/ja058344i\">10.1021\/ja058344i<\/a><\/li>\n<\/ul>\n<p>&lt;Review of NCL&gt;<\/p>\n<ul>\n<li>\u00a0Dawson, P. E.; Kent, S. B. H. <em>Annu. Rev. Biochem.<\/em> <strong>2000<\/strong>, <em>69<\/em>, 923.<\/li>\n<li>Clark, R. J.; Craik, D. J.<em> Pept. Sci.<\/em> <strong>2009<\/strong>, <em>94<\/em>, 414. DOI: <a href=\"http:\/\/dx.doi.org\/10.1002\/bip.21372\">10.1002\/bip.21372<\/a><\/li>\n<li>McGrath, N. A.; Raines, R. T. <em>Acc. Chem. Res.<\/em> <strong>2011<\/strong>, <em>44<\/em>, 752. DOI: <a href=\"http:\/\/dx.doi.org\/10.1021\/ar200081s\">10.1021\/ar200081s<\/a><\/li>\n<li>Raibaut, L.; Olivier, N.; Melnyk, O. <em>Chem. Soc. Rev.<\/em> <strong>2012<\/strong>, <em>41<\/em>, 7001. DOI: <a href=\"http:\/\/dx.doi.org\/10.1039\/C2CS35147A%20\">10.1039\/C2CS35147A\u00a0<\/a><\/li>\n<li>Wong, C. T. T.; Tung, C. L.; Li, X. <em>Mol. Biosys.<\/em> <strong>2013<\/strong>, <em>9<\/em>, 826. DOI: <a href=\"http:\/\/dx.doi.org\/10.1039\/C2MB25437A%20\">10.1039\/C2MB25437A<\/a><\/li>\n<\/ul>\n<p>&lt;General Review of Chemical Synthesis of Peptides\/Proteins<\/p>\n<ul>\n<li>Humphrey, J. M.; Chamberlin, A. R. <em>Chem. Rev.<\/em> <strong>1997<\/strong>, <em>97<\/em>, 2243. DOI: <a href=\"http:\/\/dx.doi.org\/10.1021\/cr950005s\">10.1021\/cr950005s<\/a><\/li>\n<li>Bray, B. L. <em>Nat. Rev. Drug Discov<\/em>. <strong>2003<\/strong>, <em>2<\/em>, 587. doi:<a href=\"http:\/\/dx.doi.org\/10.1038\/nrd1133\">10.1038\/nrd1133<\/a><\/li>\n<li>Nilsson, B. L.; Soellner, M. B.; Raines, R. T. <em>Annu. Rev. Biophys. Biomol. Struct.<\/em><strong>2005<\/strong>, <em>34<\/em>, 91. DOI: 10.1146\/annurev.biophys.34.040204.144700<\/li>\n<li>Kent, S. B. H. <em>Chem. Soc. Rev.<\/em> <strong>2009<\/strong>, <em>38<\/em>, 338. DOI:<a href=\"http:\/\/dx.doi.org\/10.1039\/b700141j\"> 10.1039\/b700141j<\/a><\/li>\n<li>Pattabiraman, V. R.; Bode, J. W. <em>Nature<\/em> <strong>2011<\/strong>, <em>480<\/em>, 471. doi:<a href=\"http:\/\/dx.doi.org\/10.1038\/nature10702\">10.1038\/nature1070<\/a><\/li>\n<li>\u00a0Stolzew, S. C.; Kaiser, M. <em>Synthesis<\/em> <strong>2012<\/strong>, <em>44<\/em>, 1755. DOI: <a href=\"http:\/\/dx.doi.org\/10.1055\/s-0031-1289765\">10.1055\/s-0031-1289765<\/a><\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h4>\u53cd\u5e94\u673a\u7406<\/h4>\n<p><strong><em>S<\/em>-to-<em>N<\/em>\u9170\u57fa\u8f6c\u79fb<\/strong>\u662f\u672c\u53cd\u5e94\u7684\u5173\u952e\u8fc7\u7a0b\u3002\u7b2c\u4e00\u4e2a\u786b\u916f\u4ea4\u6362\u8fc7\u7a0b\u662f\u53ef\u9006\u7684\u3002\u5373\u4f7f\u5728\u5185\u90e8\u542b\u6709\u534a\u80f1\u6c28\u9178\u4ee5\u5916\u7684\u90e8\u4f4d\u5b58\u5728\u786b\u9187\u5b98\u80fd\u56e2\uff0c\u4e5f\u4e0d\u4f1a\u5f71\u54cd\u53cd\u5e94\u3002\u4ece\u4e0d\u540c\u7684\u89d2\u5ea6\u6765\u770b\uff0c\u4e00\u5b9a\u7a0b\u5ea6\u4e0a\uff0c\u4e5f\u53ef\u4ee5\u901a\u8fc7\u4f7f\u7528\u9002\u5f53\u7684\u786b\u9187\u4f5c\u4e3a\u50ac\u5316\u5242\u6765\u52a0\u901f\u53cd\u5e94\u3002<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-17703 size-full\" src=\"https:\/\/assets.www.gsbet888.com\/uploads\/2018\/01\/NCL_1.gif\" alt=\"\" width=\"434\" height=\"154\" \/><\/p>\n<h4>\u53cd\u5e94\u5b9e\u4f8b<\/h4>\n<p>\u901a\u8fc7<a href=\"\/\/www.gsbet888.com\/reactions\/2017\/08\/%e8%bf%98%e5%8e%9f%e8%84%b1%e7%a1%ab%e5%8f%8d%e5%ba%94-reductive-desulfurization.html\">\u8fd8\u539f\u8131\u786b\u53cd\u5e94<\/a>\u3001\u53ef\u4ee5\u628aCys\u6b8b\u57fa\u9009\u62e9\u6027\u7684\u53d8\u6362\u6210Ala\u3002[1]\n<p>4-\u5def\u57fa\u82ef\u57fa\u4e59\u9178\uff08MPAA\uff09\u30012-\u5def\u57fa\u4e59\u78fa\u9178(MESNa)\u53ef\u4ee5\u4f5c\u4e3a\u50ac\u5316\u5242\u8fdb\u884c\u4f5c\u7528\u3002<\/p>\n<p>Kent\u7b49\u4eba\uff0c\u901a\u8fc7NCL\u6cd5\u5408\u6210\u4e86\u3001HIV-1\u86cb\u767d\u9176Covalent Diver\u304c[2]\u3002\u5b83\u662f\u5f53\u65f6\u7528\u5316\u5b66\u65b9\u6cd5\u5408\u6210\u7684\u6700\u5927\u7684\u80bd\uff082009\u5e74\uff09\u3002<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-17704 size-full\" src=\"https:\/\/assets.www.gsbet888.com\/uploads\/2018\/01\/NCL_3.gif\" alt=\"\" width=\"600\" height=\"322\" \/><\/p>\n<h4>\u5b9e\u9a8c\u6b65\u9aa4<\/h4>\n<p>&nbsp;<\/p>\n<h4>\u5b9e\u9a8c\u6280\u5de7<\/h4>\n<p>&nbsp;<\/p>\n<h4>\u53c2\u8003\u6587\u732e<\/h4>\n[1] Yan, L.Z.; Dawson, P.E. <em>J. Am. Chem. Soc.<\/em> <strong>2001<\/strong>, <em>123<\/em>, 526. DOI: <a href=\"http:\/\/dx.doi.org\/10.1021\/ja003265m\">10.1021\/ja003265m<\/a><br \/>\n[2] Torbeev, V. Y.; Kent, S. B. H. <em>Angew. Chem. Int. Ed.<\/em> <strong>2007<\/strong>, <em>46<\/em>, 1667. DOI: <a href=\"http:\/\/dx.doi.org\/10.1002\/anie.200604087\">10.1002\/anie.200604087<\/a><\/p>\n<p>&nbsp;<\/p>\n<h4>\u5173\u8054\u53cd\u5e94<\/h4>\n<ul class=\"list\">\n<li><a href=\"https:\/\/en.chem-station.com\/reactions-2\/2014\/02\/merrifield-solid-phase-peptide-synthesis.html\">Merrifield Solid-Phase Peptide Synthesis<\/a><\/li>\n<li><a href=\"\/\/www.gsbet888.com\/reactions\/%e7%bc%a9%e5%90%88%e5%8f%8d%e5%ba%94\/2015\/05\/%e7%bc%a9%e5%90%88%e5%89%82condensation-reagent.html\">\u7f29\u5408\u5242 Condensation Reagent<\/a><\/li>\n<li><a href=\"\/\/www.gsbet888.com\/reactions\/%e7%bc%a9%e5%90%88%e5%8f%8d%e5%ba%94\/2014\/09\/post-2589.html\">Bode Peptide Synthesis<\/a><\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h4>\u5916\u90e8\u94fe\u63a5<\/h4>\n<ul>\n<li><a href=\"https:\/\/zh.wikipedia.org\/wiki\/\u7e2e\u5408\u53cd\u61c9\">\u7f29\u5408\u53cd\u5e94<\/a>\uff08Wikipedia\uff09<\/li>\n<li><a href=\"http:\/\/en.wikipedia.org\/wiki\/Peptide\">Peptide<\/a>\uff08Wikipedia\uff09<\/li>\n<li><a href=\"http:\/\/en.wikipedia.org\/wiki\/Condensation_reaction\">Condensation Reaction<\/a>\uff08Wikjpedia\uff09<\/li>\n<li><a href=\"http:\/\/en.wikipedia.org\/wiki\/Native_chemical_ligation\">Native Chemical Ligation \u2013 Wikipedia<\/a><\/li>\n<\/ul>\n<p><strong>\u672c\u6587\u7248\u6743\u5c5e\u4e8e\u00a0<a href=\"\/\/www.gsbet888.com\/\">Chem-Station\u5316\u5b66\u7a7a\u95f4<\/a>\uff0c \u6b22\u8fce\u70b9\u51fb\u6309\u94ae\u5206\u4eab\uff0c\u672a\u7ecf\u8bb8\u53ef\uff0c\u8c22\u7edd\u8f6c\u8f7d\uff01<\/strong> <\/p>\n","protected":false},"excerpt":{"rendered":"\u6982\u8981 \u5728\u73b0\u6709\u7684\u80bd\u5408\u6210\u4e2d\uff0c\u968f\u7740\u5206\u5b50\u91cf\u7684\u589e\u52a0\uff0c\u5b98\u80fd\u56e2\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u5448\u6307\u6570\u589e\u957f\uff0c\u5e76\u4e14\u5f53\u53cd\u5e94\u70b9&#8221;\u6f5c\u5165&#8221;\u591a\u80bd\u7ed3\u6784\u5185\u90e8\uff0c\u8fd9\u6837\u5c31\u4f7f\u5f97\u540e\u7eed\u4fee\u9970\u53cd\u5e94\u66f4\u96be\u4ee5\u8fdb\u884c\u3002\u6bd4\u5982\u8bf4\uff0c\u540e\u7eed\u5982\u679c\u8981\u8fdb\u884c\u7f29\u5408\u53cd\u5e94\u4fee\u9970\u7684\u8bdd\uff0c\u53cd\u5e94\u6d3b\u6027\u4f1a\u5927\u5927\u964d\u4f4e\uff0c\u901a\u5e38\u6db2\u76f8\u53cd\u5e94\u6700\u5927\u4e5f\u53ea\u80fd\u8fde10\u4e2a\u6b8b\u57fa\uff0c\u5373\u4f7f\u662f\u56fa\u76f8\u5408\u6210\u6700\u5927\u4e5f\u5c3150\u4e2a\u6b8b\u57fa\uff0c\u5c31\u5df2\u7ecf\u5230\u4e86\u6781\u9650\u4e86\u3002 Native Chemical Ligation(NCL)\u6cd5\u53ef\u4ee5\u6709\u6548\u514b\u670d\u8fd9\u79cd\u969c\u788d\u00a0\u3002 \u5c06\u5728C-\u672b\u7aef\u5177\u6709\u786b\u916f\u7684\u80bd\u548c\u5728N-\u672b\u7aef\u5177\u6709\u672a\u4fdd\u62a4\u7684\u534a\u80f1\u6c28\u9178\u7684\u80bd\uff0c\u5728\u751f\u7269\u76f8\u5bb9\u6027\u6761\u4ef6\u4e0b(pH 7\u300120\u2103\uff5e37\u2103)\u6df7\u5408\u5c31\u53ef\u4ee5\u8fdb\u884c\u53cd\u5e94\uff0c\u5e76\u4e0d\u9700\u8981\u52a0\u5165\u591a\u4f59\u7684\u6d3b\u5316\u8bd5\u5242\u3002\u5bf9\u4e8e\u4fa7\u94fe\u65e0\u4fdd\u62a4\u7684\u591a\u80bd\u4e5f\u80fd\u9ad8\u6548\u53cd\u5e94\u5f97\u5230\u5f88\u597d\u7684\u4ea7\u7387\u3002\u8be5\u53cd\u5e94\u5229\u7528\u591a\u80bd\u4e2d\u672c\u8eab\u5c31\u5177\u6709\u7684\u5b98\u80fd\u56e2(Native Functional Group)\uff0c\u8fd9\u4e00\u70b9\u662f\u975e\u5e38\u6709\u4ef7\u503c\u7684\u3002\u901a\u8fc7\u8fd9\u79cd\u65b9\u6cd5\uff0c\u53ef\u4ee5\u5316\u5b66\u5408\u6210\u9ad8\u8fbe\u7ea6200\u4e2a\u6b8b\u57fa\u7684\u80bd\u94fe\u3002 &nbsp; \u57fa\u672c\u6587\u732e Dawson, P. E.; Muir, T. W.; Clark-Lewis, I.; Kent, S. B. H. Science 1994, 266, 776. DOI:10.1126\/science.7973629 Johnson, E. C. B.; Kent, S. B. H. J. Am. Chem. Soc. 2006, 128, 6640. DOI: 10.1021\/ja058344i &lt;Review of NCL&gt; \u00a0Dawson, P. E.; Kent, S. B. H. Annu. Rev. Biochem. 2000, 69, 923. Clark, R. J.; Craik, D. J. Pept. Sci. 2009, 94, 414. DOI: 10.1002\/bip.21372 McGrath, N. A.; Raines, R. T. Acc. Chem. Res. 2011, 44, 752. DOI: 10.1021\/ar200081s Raibaut, L.; Olivier, N.; Melnyk, O. Chem. Soc. Rev. 2012, 41, 7001. DOI: 10.1039\/C2CS35147A\u00a0 Wong, C. T. T.; Tung, C. L.; Li, [&hellip;]","protected":false},"author":5,"featured_media":17702,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","enabled":false},"version":2}},"categories":[2,12],"tags":[344,2186],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/assets.www.gsbet888.com\/uploads\/2018\/01\/2014-10-30_01-59-00.png","jetpack_shortlink":"https:\/\/wp.me\/p96op1-4Bv","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/posts\/17701"}],"collection":[{"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/comments?post=17701"}],"version-history":[{"count":9,"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/posts\/17701\/revisions"}],"predecessor-version":[{"id":27186,"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/posts\/17701\/revisions\/27186"}],"wp:featuredmedia":[{"embeddable":true,"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/media\/17702"}],"wp:attachment":[{"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/media?parent=17701"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/categories?post=17701"},{"taxonomy":"post_tag","embeddable":true,"href":"\/\/www.gsbet888.com\/wp-json\/wp\/v2\/tags?post=17701"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}