Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Chemistry, Engineering and Medicine for Human Health (ChEM-H) Institute, Stanford University, Stanford, CA 94305, USA.
STAR Protoc. 2021 Jan 12;2(1):100263. doi: 10.1016/j.xpro.2020.100263. eCollection 2021 Mar 19.
Targeted drug delivery to pancreatic islet β cells is an unmet clinical need. β cells possess a uniquely high Zn concentration, and integrating Zn-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 Zn, 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 Horton et al. (2019).
将药物靶向递送至胰岛β细胞是未满足的临床需求。β细胞具有独特的高锌浓度，将锌结合活性整合到小分子中可以使药物在β细胞中的积累和活性发生偏向。本方案可用于评估分子螯合胰岛锌、在胰岛中积累以及刺激小鼠胰腺中β细胞选择性复制的能力。一个障碍是建立基于 LC-MS/MS 的化合物测量方法。限制包括目标化合物的离子化能力和一些实验测定步骤的时间敏感性。有关该方案使用和执行的完整详细信息，请参阅 Horton 等人。（2019 年）。
