Generation of Reactive Oxygen Species by Photosensitizers and their Modes of Action on Proteins

Author(s): Itzhak Bilkis, Israel Silman, Lev Weiner*.

Journal Name: Current Medicinal Chemistry

Volume 25 , Issue 40 , 2018

Abstract:

In this review, we first survey the mechanisms underlying the chemical modification of amino acid residues in proteins by singlet oxygen elicited by photosensitizers. Singlet oxygen has the capacity to cause widespread chemical damage to cellular proteins. Its use in photodynamic therapy of tumors thus requires the development of methodologies for specific addressing of the photosensitizer to malignant cells while sparing normal tissue. We describe three targeting paradigms for achieving this objective. The first involves the use of a photosensitizer with a high affinity for its target protein; in this case, the photosensitizer is methylene blue for acetylcholinesterase. The second paradigm involves the use of the hydrophobic photosensitizer hypericin, which has the capacity to interact selectively with partially unfolded forms of proteins, including nascent species in rapidly dividing or virus-infected and cancer cells, acting preferentially at membrane interfaces. In this case, partially unfolded molten globule species of acetylcholinesterase serve as the model system. In the third paradigm, the photodynamic approach takes advantage of a general approach in ‘state-of-the-art’ chemotherapy, by coupling the photosensitizer emodin to a specific peptide hormone, GnRH, which recognizes malignant cells via specific GnRH receptors on their surface.

Keywords: Singlet oxygen, photosensitizer, amino acid oxidation, acetylcholinesterase, cancer, drug targeting, peptide hormone.

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Article Details

VOLUME: 25
ISSUE: 40
Year: 2018
Page: [5528 - 5539]
Pages: 12
DOI: 10.2174/0929867325666180104153848
Price: $58

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