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The past, present, and future of artificial zinc finger proteins: design strategies and chemical and biological applications.

ABSTRACT: Zinc finger proteins are abundant in the human proteome and are responsible for a variety of functions. The domains that constitute zinc finger proteins are compact spherical structures, each comprising approximately 30 amino acid residues, but they also have precise molecular factor functions: zinc binding and DNA recognition. Due to the biological importance of zinc finger proteins and their unique structural and functional properties, many artificial zinc finger proteins have been created and are expected to improve their functions and biological applications. In this study, we review previous studies on the redesign and application of artificial zinc finger proteins, focusing on the experimental results obtained by our research group. In addition, we systematically review various design strategies used to construct artificial zinc finger proteins and discuss in detail their potential biological applications, including gene editing. This review will provide relevant information to researchers involved or interested in the field of artificial zinc finger proteins as a potential new treatment for various diseases.

SUBMITTER: Negi S

PROVIDER: S-EPMC9903285 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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The past, present, and future of artificial zinc finger proteins: design strategies and chemical and biological applications.

Negi Shigeru S Imanishi Miki M Hamori Mami M Kawahara-Nakagawa Yuka Y Nomura Wataru W Kishi Kanae K Shibata Nobuhito N Sugiura Yukio Y

Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 20230207 3

Zinc finger proteins are abundant in the human proteome and are responsible for a variety of functions. The domains that constitute zinc finger proteins are compact spherical structures, each comprising approximately 30 amino acid residues, but they also have precise molecular factor functions: zinc binding and DNA recognition. Due to the biological importance of zinc finger proteins and their unique structural and functional properties, many artificial zinc finger proteins have been created and ...[more]

PMID: 36749405

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Project description:Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that prevents administration of the full efficacious dosage and often leads to treatment withdrawal. Peripheral sensory neurotoxicity varies from paresthesia in fingers to ataxic gait, which might be transient or irreversible. Because the number of patients being treated with these neurotoxic agents is still increasing, the need for understanding the pathogenesis of this dramatic side effect is critical. Platinum derivatives, such as cisplatin and carboplatin, harm mainly peripheral nerves and dorsal root ganglia neurons, possibly because of progressive DNA-adduct accumulation and inhibition of DNA repair pathways (e.g., extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 mitogen-activated protein kinass), which finally mediate apoptosis. Oxaliplatin, with a completely different pharmacokinetic profile, may also alter calcium-sensitive voltage-gated sodium channel kinetics through a calcium ion immobilization by oxalate residue as a calcium chelator and cause acute neurotoxicity. Polymorphisms in several genes, such as voltage-gated sodium channel genes or genes affecting the activity of pivotal metal transporters (e.g., organic cation transporters, organic cation/carnitine transporters, and some metal transporters, such as the copper transporters, and multidrug resistance-associated proteins), can also influence drug neurotoxicity and treatment response. However, most pharmacogenetics studies need to be elucidated by robust evidence. There are supportive reports about the effectiveness of several neuroprotective agents (e.g., vitamin E, glutathione, amifostine, xaliproden, and venlafaxine), but dose adjustment and/or drug withdrawal seem to be the most frequently used methods in the management of platinum-induced peripheral neurotoxicity. To develop alternative options in the treatment of platinum-induced neuropathy, studies on in vitro models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution.

Dataset Information

The past, present, and future of artificial zinc finger proteins: design strategies and chemical and biological applications.

Publications

The past, present, and future of artificial zinc finger proteins: design strategies and chemical and biological applications.

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