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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Notes
ZnTalkyl-2,3,4-PyP5+ Zn(II) meso-tetrakis(N-alkylpyridinium-2 or 3-yl)porphyrin, alkyl being methyl (ZnTM-2-PyP, ZnTM-3-PyP, ZnTM-4-PyP), ethyl (ZnTE-2-PyP), n-butyl (ZnTnBu-2-PyP), and n-hexyl (ZnTnHex-2-PyP) 2, 3, and 4 relate to ortho, meta, and para isomers, respectively. Hematoporphyrin D, HpD.
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LB and JC are grateful for the financial support by grants MB 07/04, MB 03/07, and YM 02/08 from Kuwait University and to Research Core Facility (GM01/01 and GM01/05). IBH acknowledges the support from NIH U19 AI67798, Wallace H Coulter Translational Partners Grant Program, and NIH-IR21-ESO/3682. The authors are grateful to Dr. Irwin Fridovich for his guidance, ideas and continuous help.
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Benov, L., Craik, J. & Batinic-Haberle, I. Protein damage by photo-activated Zn(II) N-alkylpyridylporphyrins. Amino Acids 42, 117–128 (2012). https://doi.org/10.1007/s00726-010-0640-1
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DOI: https://doi.org/10.1007/s00726-010-0640-1