Stereochemical factors in the transport and binding of photosensitizers in biological systems and in photodynamic therapy.
The uptake and biological activity of porphyrins and phthalocyanines in tumours were correlated with the geometrical features of the photosensitizer molecules. The data suggest that a critical distance of approximately 1.2 nm between oxygen atoms (originating in SO3-, COO- or OH substituents) characterizes a biologically active photosensitizer for photodynamic therapy. We propose that tubulin, which is available in large amounts during mitosis, is the main receptor molecule which binds these photosensitizers. Basic amino acid residues or tightly bound cations in tubulin or homologous proteins may act as binding sites on the receptor molecule.
Winkelman
J W
JW
Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Arad
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D
Kimel
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D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002147:Calmodulin / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D054833:Isoindoles; D008958:Models, Molecular; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism*; D010860:Pigments, Biological / Q000737:chemistry / Q000378:metabolism; D011166:Porphyrins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D010860:Pigments, Biological; D011166:Porphyrins; D014404:Tubulin; C013647:phthalocyanine