Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Why Hydrogen Peroxide-Producing Proteins are not suitable Targets for Drug Development

Version 1 : Received: 26 March 2024 / Approved: 26 March 2024 / Online: 27 March 2024 (07:52:45 CET)

How to cite: Sakanyan, V.; Sousa, R.A.D. Why Hydrogen Peroxide-Producing Proteins are not suitable Targets for Drug Development. Preprints 2024, 2024031622. https://doi.org/10.20944/preprints202403.1622.v1 Sakanyan, V.; Sousa, R.A.D. Why Hydrogen Peroxide-Producing Proteins are not suitable Targets for Drug Development. Preprints 2024, 2024031622. https://doi.org/10.20944/preprints202403.1622.v1

Abstract

Reactive oxygen species (ROS) play an important role in biological processes and offer hope for the development of effective treatments for ROS-dependent diseases, including cancer. The interaction of hydrogen peroxide with proteins stimulates the creation of chemical molecules that can weaken or stop the pathological process in cancer. However, reliable drugs have not yet been described. To understand the reason for the failure, we studied the behavior of ROS-containing compounds in cancer cells. The epidermal growth factor receptor (EGFR) is activated by interaction with a ligand protein, as well as by binding the chemical structure of hydrogen peroxide to the catalytic cysteine in the intracellular domain. Both mechanisms trigger signaling pathways in cells. The EGFR can be inactivated by protein tyrosinase phosphatase PTP-1B, which itself is activated by hydrogen peroxide. A simple in-gel fluorescence technique was used to demonstrate the rapid binding of hydrogen peroxide to a large number of proteins, including both activating and inactivating target proteins. Natural defense systems take longer to action and apparently cannot prevent hydrogen peroxide from binding to protect cells from exposure to unwanted proteins. Therefore, superoxide dismutase, which produces hydrogen peroxide, is not a suitable target for disease therapy.

Keywords

Reactive oxygen species; hydrogen peroxide; superoxide dismutase; epidermal growth factor receptor; redox therapy; cancer

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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