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Protocol for determining zinc-dependent ? cell-selective small-molecule delivery in mouse pancreas.

ABSTRACT: Targeted drug delivery to pancreatic islet ? cells is an unmet clinical need. ? cells possess a uniquely high Zn²⁺ concentration, and integrating Zn²⁺-binding activity into a small molecule can bias drug accumulation and activity toward ? cells. This protocol can be used to evaluate a molecule's capacity to chelate islet Zn²⁺, accumulate in islets, and stimulate ? 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).

SUBMITTER: Horton TM

PROVIDER: S-EPMC7806521 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Protocol for determining zinc-dependent β cell-selective small-molecule delivery in mouse pancreas.

Horton Timothy M TM Kraemer Benjamin R BR Annes Justin P JP

STAR protocols 20210112 1

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 ...[more]

PMID: 33490979

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