Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand

摘要

Abstract > The protein Survivin is highly upregulated in most cancers and considered to be a key player in carcinogenesis. We explored a supramolecular approach to address Survivin as a drug target by inhibiting the protein–protein interaction of Survivin and its functionally relevant binding partner Histone H3. Ligand L1 is based on the guanidiniocarbonyl pyrrole cation and serves as a highly specific anion binder in order to target the interaction between Survivin and Histone H3. NMR titration confirmed binding of L1 to Survivin's Histone H3 binding site. The inhibition of the Survivin–Histone H3 interaction and consequently a reduction of cancer cell proliferation were demonstrated by microscopic and cellular assays. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> > 蛋白质Survivin在大多数癌症中高度上调，并且被认为是致癌物中的关键球员。我们探讨了一种超分子方法来通过抑制Survivin的蛋白质 - 蛋白质相互作用及其功能相关的结合伴侣组蛋白H3来解决Survivin作为药物靶标的方法。配体 l1 </ b> 基于胍基羰基吡咯阳离子，用作高度特异性的阴离子粘合剂，以靶向Survivin和组蛋白H3之间的相互作用。 NMR滴定证实了绑定 l1 </ b> 对Survivin的组蛋白H3结合位点。通过微观和细胞测定证明了Survivin-ModyOper H3相互作用及因此降低了癌细胞增殖的降低。 </ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-19011/'>《Angewandte Chemie》</a> <b style="margin: 0 2px;">|</b><span>2020年第14期</span><b style="margin: 0 2px;">|</b><span>共5页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1188.html" title="应用化学">应用化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cancer&option=203" rel="nofollow">cancer;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=molecular recognition&option=203" rel="nofollow">molecular recognition;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=PPI inhibitors&option=203" rel="nofollow">PPI inhibitors;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=supramolecular chemistry&option=203" rel="nofollow">supramolecular chemistry;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=survivin&option=203" rel="nofollow">survivin;</a> </p> <div class="translation"> 机译：癌症;分子识别;PPI抑制剂;超分子化学;Survivin; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704028161440.html">Functional Disruption of the Cancer‐Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> </a> <a href="/journal-foreign-19011/" target="_blank" rel="nofollow" class="tuijian_authcolor">Angewandte Chemie .</a> <span>2020</span><span>,第14期</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：Survivin和组蛋白H3与胍基内尼羰基吡咯配体的癌症相关相互作用的功能破坏</span> </p> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/0704018625036.html">CAF-1-induced oligomerization of histones H3/H4 and mutually exclusive interactions with Asf1 guide H3/H4 transitions among histone chaperones and DNA</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Liu Wallace H.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Liu Wallace H.,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Roemer Sarah C.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Roemer Sarah C.,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Port Alex M.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Port Alex M.,</a> <a href="/journal-foreign-26058/" target="_blank" rel="nofollow" class="tuijian_authcolor">Nucleic Acids Research .</a> <span>2012</span><span>,第22期</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：CAF-1诱导的组蛋白H3 / H4寡聚以及与Asf1的互斥相互作用指导组蛋白伴侣和DNA之间的H3 / H4过渡</span> </p> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-foreign_detail_thesis/0204118863166.html">CAF-1-induced oligomerization of histones H3/H4 and mutually exclusive interactions with Asf1 guide H3/H4 transitions among histone chaperones and DNA</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Alex M. 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