Sidechain Engineering in Cell-Penetrating Poly(disulfide)s
Sidechain Engineering in Cell-Penetrating Poly(disulfide)s
复制标题
细胞穿透聚（二硫化物）中的侧链工程
DOI：
--
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
S. Matile
中科院分区：
文献类型：
--
作者：
P. Morelli;S. Matile
细胞穿透型聚二硫化物（CPDs）是近年来研究进入细胞的新方法。在本报告中，我们揭示了一种共价修饰cpd侧链的通用方法。证明了铜催化的炔叠氮化环加成反应（CuAAC）与不同环张力的应变环二硫化物或增加胍和磷阳离子的相容性。以二硫环张力重新加载CPDs，其活性至少增加20倍，并保留了对Ellman试剂抑制的敏感性。通过侧链工程积累永久正电荷，使ellman不敏感的cpd具有类似的活性增加。共定位实验表明，CPDs可以到达核内体、细胞质和细胞核，这取决于它们的性质和浓度。在相关对照的支持下，这些趋势证实了CPDs是通过反离子和硫醇介导的摄取结合而起作用的，并且两者之间的平衡可以合理控制。对于最活跃的cpd，可以在低至5 nM的底物（荧光团）浓度下观察到摄取。
Cell-penetrating poly(disulfide)s (CPDs) have been introduced recently to explore new ways to enter into cells. In this report, we disclose a general method to covalently modify the sidechains of CPDs. Compatibility of copper-catalyzed alkyne-azide cycloaddition (CuAAC) with the addition of either strained cyclic disulfides of varied ring tension or increasing numbers of guanidinium and phosphonium cations is demonstrated. Reloading CPDs with disulfide ring tension results in an at least 20-fold increase in activity with preserved sensitivity toward inhibition with the Ellman's reagent. The cumulation of permanent positive charges by sidechain engineering affords Ellman-insensitive CPDs with similarly increased activity. Co-localization experiments indicate the CPDs reach endosomes, cytosol and nucleus, depending on their nature and their concentration. Supported by pertinent controls, these trends confirm that CPDs operate with combination of counterion- and thiol-mediated uptake, and that the balance between the two can be rationally controlled. For the most active CPDs, uptake can be observed at substrate (fluorophore) concentrations as low as 5 nM.
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DOI：
10.1021/jz100248c
发表时间：
2010
期刊：
The journal of physical chemistry letters
影响因子：
--
作者：
Jablonski AE;Kawakami T;Ting AY;Payne CK
通讯作者：
Payne CK
影响因子：
5.1
作者：
Kim, Tae-il;Kim, Sung Wan
通讯作者：
Kim, Sung Wan
影响因子：
16.6
作者：
Li, Mao;Schlesiger, Stefanie;Schmuck, Carsten
通讯作者：
Schmuck, Carsten
影响因子：
8.4
作者：
Clare S. Mahon;D. Fulton
通讯作者：
Clare S. Mahon;D. Fulton
影响因子：
4.6
作者：
Oupicky, David;Li, Jing
通讯作者：
Li, Jing