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Isothermal kinase-triggered supramolecular assemblies as drug sensitizers.

ABSTRACT: Protein kinases, the main regulators of a vast map of cellular processes, are the most attractive targets in drug discovery. Despite a few successful examples of protein kinase inhibitors, the drug discovery strategy of downregulating protein kinase activity has been quite limited and often fails even in animal models. Here, we utilize protein kinase A (PKA) activity to design PKA-triggered supramolecular assemblies with anticancer activities. Grafting a suitable peptide to PNIPAM raises the critical temperature of the LCST polymer above body temperature. Interestingly, the corresponding phosphorylated polymer has a critical temperature below body temperature, making this peptide-appended PNIPAM a suitable polymer for the PKA-triggered supramolecular assembly process. PKA-triggered assembly occurs selectively in PKA-upregulated MCF-7 cells, which disturbs the cytoskeleton and sensitizes cancer cells against doxorubicin. The chemosensitization is also observed in vivo to identify effective tumor inhibitors with satisfactory biocompatibility. Overall, this phosphorylation-induced (in principle, PKA-catalyzed) supramolecular assembly opens up a promising chemotherapy strategy for combating kinase-upregulated cancer.

SUBMITTER: Liu D

PROVIDER: S-EPMC8145944 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Isothermal kinase-triggered supramolecular assemblies as drug sensitizers.

Liu Dongdong D Miao Zhe Z Wu Chengling C He Fangfei F Ren Peng P Bai Shuo S Jiang Xingyu X Gao Yuan Y

Chemical science 20191206 4

Protein kinases, the main regulators of a vast map of cellular processes, are the most attractive targets in drug discovery. Despite a few successful examples of protein kinase inhibitors, the drug discovery strategy of downregulating protein kinase activity has been quite limited and often fails even in animal models. Here, we utilize protein kinase A (PKA) activity to design PKA-triggered supramolecular assemblies with anticancer activities. Grafting a suitable peptide to PNIPAM raises the cri ...[more]

PMID: 34084370

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Dataset Information

Isothermal kinase-triggered supramolecular assemblies as drug sensitizers.

Publications

Isothermal kinase-triggered supramolecular assemblies as drug sensitizers.

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