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
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