Protein damage by photo-activated Zn(II) N-alkylpyridylporphyrins |
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Authors: | Ludmil Benov James Craik Ines Batinic-Haberle |
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Institution: | (1) Department of Biochemistry, Faculty of Medicine, Kuwait University, P. O. Box 24923, 13110 Safat, Kuwait;(2) Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA |
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Abstract: | Destruction of unwanted cells and tissues in photodynamic therapy (PDT) is achieved by a combination of light, oxygen, and
light-sensitive molecules. The advantages of PDT compared to other traditional treatment modalities, and the shortcomings
of the currently used photosensitizers, have stimulated the search for new, more efficient photosensitizer candidates. Ability
to inflict selective damage to particular proteins through photo-irradiation would significantly advance the design of highly
specific photosensitizers. Achieving this objective requires comprehensive knowledge concerning the interactions of the particular
photosensitizer with specific targets. Here, we summarize the effects of Zn(II) N-alkylpyridylporphyrin-based photosensitizers on intracellular (metabolic, antioxidant and mitochondrial enzymes) and membrane
proteins. We emphasize how the structural modifications of the porphyrin side substituents affect their lipophilicity, which
in turn influence their subcellular localization. Thus, Zn(II) N-alkylpyridylporphyrins target particular cellular sites and proteins of interest, and are more efficient than hematoporphyrin
D, whose commercial preparation (Photofrin) has been clinically approved for PDT. |
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Keywords: | |
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