Girard's reagent P derivative of beta-Apo-8'-carotenal: a potent photoprotective agent.
A cationic carotenoid derivative (GRP-carotenal) was synthesized by the reaction of Girard's reagent P and beta-apo-8'-carotenal. The singlet-oxygen quenching constants for GRP-carotenal were 1.3 +/- 0.1 x 10(10) and 1.0 +/- 0.1 x 10(10) M-1 s-1 in acetonitrile and in detergent micelles, respectively. Photosensitized damage to K562 leukemia cells from cis-di(4-sulfonatophenyl)diphenylporphine, hypericin and protoporphyrin IX was inhibited by GRP-carotenal under conditions where beta-apo-8'-carotenal, beta-carotene and crocetin were ineffective. The unique cytoprotective properties of GRP-carotenal, relative to the other carotenoids studied, could not be explained by the differences in the cell content of the various carotenoids or by the changes in the cell content of the photosensitizers used. Photosensitizer fluorescence from labeled K562 cells was reduced by GRP-carotenal but not by the other carotenoids studied. The novel photoprotective properties of GRP-carotenal may be due to its subcellular distribution. In photosensitizer-containing detergent micelles, novel properties of GRP-carotenal were not apparent. None of the carotenoids studied reduced photosensitizer fluorescence or singlet-oxygen generation. Singlet-oxygen quenching by GRP-carotenal and by beta-apo-8'-carotenal were roughly the same. Crocetin has a singlet-oxygen quenching constant that is about a factor of five lower. Singlet-oxygen quenching by beta-carotene was limited by its aggregation.
Kanofsky
J R
JR
Medical Service, Edward Hines Jr., Department of Veterans Affairs Hospital, Hines, IL, USA. jeff.kanofsky@med.va.gov
Sima
P D
PD
D000873:Anthracenes; D002338:Carotenoids / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D020014:K562 Cells / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D010569:Perylene / Q000031:analogs & derivatives* / Q000633:toxicity; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000633:toxicity; D011166:Porphyrins / Q000633:toxicity; D011524:Protoporphyrins / Q000633:toxicity; D026082:Singlet Oxygen; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014801:Vitamin A / Q000031:analogs & derivatives
D000873:Anthracenes; C425083:GRP-carotenal; D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; C425082:di(4-sulfonatophenyl)diphenylporphine; C487773:trans-sodium crocetinate; D014801:Vitamin A; D026082:Singlet Oxygen; D002338:Carotenoids; D010569:Perylene; C004965:hypericin; C028025:protoporphyrin IX; D010100:Oxygen; C004984:apocarotenal