Fluorescent probes of the apoptolidins and their utility in cellular localization studies.
Fluorescent probes of the apoptolidins and their utility in cellular localization studies.
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DOI：
10.1002/anie.201408906
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发表时间：
2015-01-12
影响因子：
16.6
通讯作者：
Sulikowski, Gary A.
中科院分区：
文献类型：
--
作者：
DeGuire, Sean M.;Earl, David C.;Du, Yu;Crews, Brenda A.;Jacobs, Aaron T.;Ustione, Alessandro;Daniel, Cristina;Chong, Katherine M.;Marnett, Lawrence J.;Piston, David W.;Bachmann, Brian O.;Sulikowski, Gary A.
Apopolidin A 被描述为 NCI 60 细胞系面板中待评估的前 0.1% 最具细胞选择性的细胞毒剂之一。 apoptolidin A 的分子结构由 20 元大环内酯组成，单糖部分和二糖部分分别位于 C9 和 C27。与 apoptolidin A 相比，在针对多种肿瘤细胞系进行评估时，糖苷配基（apoptolidinone）没有表现出细胞毒性（>10 μM）。 Apoptolidin H 是 apoptolidin A 的 C27 去糖基化类似物，是通过靶向糖基转移酶基因缺失产生的，对 H292 肺癌细胞表现出亚微摩尔活性。细胞凋亡素 A 和 H 的 C2' 羟基与 5-叠氮基戊酸的选择性酯化提供了叠氮基官能化衍生物，其效力与其母体大环内酯相同。叠氮基凋亡素很容易经历应变促进的炔叠氮环加成 (SPAAC) 反应，以提供荧光和生物素功能化探针。显微镜研究表明凋亡素 A 和 H 定位于 H292 人肺癌细胞的线粒体中。
Apoptolidin A has been described as among the top 0.1% most cell selective cytotoxic agents to be evaluated in the NCI 60 cell line panel. The molecular structure of apoptolidin A consists of a 20-membered macrolide with mono- and disaccharide moieties located at C9 and C27, respectively. In contrast to apoptolidin A, the aglycone (apoptolidinone) shows no cytotoxicity (>10 μM) when evaluated against several tumor cell lines. Apoptolidin H, the C27 deglycosylated analog of apoptolidin A, was produced by targeted glycosyl transferase gene deletion and displayed sub-micromolar activity against H292 lung carcinoma cells. Selective esterification of the C2′ hydroxyl group of apoptolidins A and H with 5-azidopentanoic acid afforded azido functionalized derivatives of potency equal to their parent macrolide. Azido apoptolidins readily underwent strain-promoted alkyne azido cycloaddition (SPAAC) reactions to provide access to fluorescent and biotin functionalized probes. Microscopy studies demonstrate apoptolidins A and H localize in the mitochondria of H292 human lung carcinoma cells.
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影响因子：
2.1
作者：
Du Y;Derewacz DK;Deguire SM;Teske J;Ravel J;Sulikowski GA;Bachmann BO
通讯作者：
Bachmann BO
影响因子：
15
作者：
Hayakawa, Y;Kim, JW;Seto, H
通讯作者：
Seto, H
丙酮酸激酶M2激活剂促进四聚体形成并抑制肿瘤发生。
影响因子：
14.8
作者：
Anastasiou, Dimitrios;Yu, Yimin;Israelsen, William J.;Jiang, Jian-Kang;Boxer, Matthew B.;Hong, Bum Soo;Tempel, Wolfram;Dimov, Svetoslav;Shen, Min;Jha, Abhishek;Yang, Hua;Mattaini, Katherine R.;Metallo, Christian M.;Fiske, Brian P.;Courtney, Kevin D.;Malstrom, Scott;Khan, Tahsin M.;Kung, Charles;Skoumbourdis, Amanda P.;Veith, Henrike;Southall, Noel;Walsh, Martin J.;Brimacombe, Kyle R.;Leister, William;Lunt, Sophia Y.;Johnson, Zachary R.;Yen, Katharine E.;Kunii, Kaiko;Davidson, Shawn M.;Christofk, Heather R.;Austin, Christopher P.;Inglese, James;Harris, Marian H.;Asara, John M.;Stephanopoulos, Gregory;Salituro, Francesco G.;Jin, Shengfang;Dang, Lenny;Auld, Douglas S.;Park, Hee-Won;Cantley, Lewis C.;Thomas, Craig J.;Heiden, Matthew G. Vander
通讯作者：
Heiden, Matthew G. Vander
影响因子：
2.7
作者：
Jiang, Jian-kang;Boxer, Matthew B.;Vander Heiden, Matthew G.;Shen, Min;Skoumbourdis, Amanda P.;Southall, Noel;Veith, Henrike;Leister, William;Austin, Christopher P.;Park, Hee Won;Inglese, James;Cantley, Lewis C.;Auld, Douglas S.;Thomas, Craig J.
通讯作者：
Thomas, Craig J.
影响因子：
15
作者：
Kim, Yun Kyung;Ha, Hyung-Ho;Chang, Young-Tae
通讯作者：
Chang, Young-Tae