Site-directed photoproteolysis of 8-oxoguanine DNA glycosylase 1 (OGG1) by specific porphyrin-protein probe conjugates: a strategy to improve the effectiveness of photodynamic therapy for cancer.
The specific light-induced, non-enzymatic photolysis of mOGG1 by porphyrin-conjugated or rose bengal-conjugated streptavidin and porphyrin-conjugated or rose bengal-conjugated first specific or secondary anti-IgG antibodies is reported. The porphyrin chlorin e6 and rose bengal were conjugated to either streptavidin, rabbit anti-mOGG1 primary specific antibody fractions or goat anti-rabbit IgG secondary antibody fractions. Under our experimental conditions, visible light of wavelengths greater than 600 nm induced the non-enzymatic degradation of mOGG1 when this DNA repair enzyme either directly formed a complex with chlorin e6-conjugated anti-mOGG1 primary specific antibodies or indirectly formed complexes with either streptavidin-chlorin e6 conjugates and biotinylated first specific anti-mOGG1 antibodies or first specific anti-mOGG1 antibodies and chlorin e6-conjugated anti-rabbit IgG secondary antibodies. Similar results were obtained when rose bengal was used as photosensitizer instead of chlorin e6. The rate of the photochemical reaction of mOGG1 site-directed by all three chlorin e6 antibody complexes was not affected by the presence of the singlet oxygen scavenger sodium azide. Site-directed photoactivatable probes having the capacity to generate reactive oxygen species (ROS) while destroying the DNA repair system in malignant cells and tumors may represent a powerful strategy to boost selectivity, penetration and efficacy of current photodynamic (PDT) therapy methodologies.
Conlon
Kimberly A
KA
Department of Pharmacological Sciences, School of Medicine, University Hospital and Medical Center, State University of New York, Stony Brook, NY 11794-8651, USA. conlon@pharm.sunysb.edu
Berrios
Miguel
M
D000818:Animals; D002735:Chlorophyllides; D045647:DNA Glycosylases / Q000528:radiation effects*; D006801:Humans; D008027:Light; D023421:Models, Animal; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy; D010782:Photolysis; D011166:Porphyrins / Q000378:metabolism* / Q000494:pharmacology; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012395:Rose Bengal
D002735:Chlorophyllides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D012395:Rose Bengal; C062985:phytochlorin; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human