CHEMISTRY OF HEMATOPORPHYRIN-DERIVED PHOTOSENSITIZERS |
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| Authors: | David Kessel Paul Thompson Brian Musselman C K Chang |
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| Institution: | Departments of Medicine and Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA;Departments of Biochemistry, Michigan State University, East Lansing MI 48823, USA;Departments of Chemistry, Michigan State University, East Lansing MI 48823, USA |
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| Abstract: | Abstract The hematoporphyrin-derived tumor-localizing preparation HPD consists of porphyrin monomers, which are'inactive'(not tumor-localizing), and a dimer/oligomer fraction which is responsible for the localizing phenomenon. In an organic solvent system, gel-exclusion chromatography can separate HPD into fractions containing porphyrin monomers, dimers or oligomers. The relative amount of the dimer/oligomer fraction of HPD was a function of the pH of the mixture used to transform HP mono/di acetate to HPD. HPD prepared by the'Upson'procedure contained dimer/oligomer linkages which are labile to 1 M NaOH (in 50% tetrahydrofuran), and are reduced by LiAlH4 to alcohols. These properties are characteristic of esters. But a commercial product, Photofrin II, contained approx. 50% of material refractory to both reagents described above. This behavior is characteristic of an ether linkage. These observations show that the nature of the linkage joining the porphyrin units is sensitive to conditions employed in HPD preparation. Tumor localization derives, in part, from affinity of these oligomers for plasma lipoprotein, and is associated with conformational alterations characteristic of these porphyrin-porphyrin linkages. |
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