Protocol for determining zinc-dependent β cell-selective small-molecule delivery in mouse pancreas.
Protocol for determining zinc-dependent β cell-selective small-molecule delivery in mouse pancreas.
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DOI：
10.1016/j.xpro.2020.100263
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发表时间：
2021-03-19
期刊：
影响因子：
--
通讯作者：
Annes JP
中科院分区：
文献类型：
--
作者：
Horton TM;Kraemer BR;Annes JP
靶向给药胰岛β细胞是一个尚未满足的临床需求。β细胞具有独特的高Zn2+浓度，将Zn2+结合活性整合到小分子中可以使药物的积累和活性偏向β细胞。该方案可用于评估分子螯合胰岛Zn2+的能力，在胰岛积累，并刺激小鼠胰腺β细胞选择性复制。其中一个障碍是建立基于LC-MS/ ms的化合物测定方法。限制包括目标化合物的电离性和一些实验分析步骤的时间敏感性。有关使用和执行本协议的完整详情，请参阅。胰岛Zn2+螯合作用可通过LC-MS/MS评估胰岛螯合物积累可通过高含量细胞成像评估β细胞选择性复制可通过高含量细胞成像评估靶向给药胰岛β细胞是一个未满足的临床需求。β细胞具有独特的高Zn2+浓度，将Zn2+结合活性整合到小分子中可以使药物的积累和活性偏向β细胞。该方案可用于评估分子螯合胰岛Zn2+的能力，在胰岛积累，并刺激小鼠胰腺β细胞选择性复制。其中一个障碍是建立基于LC-MS/ ms的化合物测定方法。限制包括目标化合物的电离性和一些实验分析步骤的时间敏感性。
Targeted drug delivery to pancreatic islet β cells is an unmet clinical need. β cells possess a uniquely high Zn2+ concentration, and integrating Zn2+-binding activity into a small molecule can bias drug accumulation and activity toward β cells. This protocol can be used to evaluate a molecule’s capacity to chelate islet Zn2+, accumulate in islets, and stimulate β cell-selective replication in mouse pancreas. One obstacle is establishing an LC-MS/MS-based method for compound measurement. Limitations include target compound ionizability and the time-sensitive nature of some experimental assay steps. For complete details on the use and execution of this protocol, please refer to. Protocol to measure zinc-dependent β cell-selective small-molecule delivery Islet Zn2+ chelation assessed by fluorescence microscopy via TSQ competition Islet chelator accumulation can be assessed by LC-MS/MS β cell-selective replication can be assessed by high-content cell imaging Targeted drug delivery to pancreatic islet β cells is an unmet clinical need. β cells possess a uniquely high Zn2+ concentration, and integrating Zn2+-binding activity into a small molecule can bias drug accumulation and activity toward β cells. This protocol can be used to evaluate a molecule’s capacity to chelate islet Zn2+, accumulate in islets, and stimulate β cell-selective replication in mouse pancreas. One obstacle is establishing an LC-MS/MS-based method for compound measurement. Limitations include target compound ionizability and the time-sensitive nature of some experimental assay steps.
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影响因子：
16.6
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DOI：
10.1073/pnas.1201149109
发表时间：
2012-03-06
影响因子：
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作者：
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通讯作者：
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