title: Antibody-catalyzed oxidative degradation of nicotine using riboflavin.
abstract: Tobacco abuse remains a major cause of death worldwide despite ample evidence linking nicotine to various disease states. Consequently, immunopharmacotherapeutic approaches for the treatment of nicotine abuse have received increasing attention. Although a number of nicotine-binding antibodies have been disclosed, no antibody catalysts exist which efficiently degrade nicotine into pharmacologically inactive substances. Herein, we report the first catalytic antibodies which can oxidatively degrade nicotine. These biocatalysts use the micronutrient riboflavin and visible light as a source of singlet oxygen for the production of reactive oxygen species. Along with various known nicotine metabolites, antibody-catalyzed nicotine oxidations produce two novel nicotine oxidation products that were also detected in control ozonation reactions of nicotine. The reaction is efficient, with multiple turnovers of catalyst observed and total consumption of nicotine attained. These results demonstrate the potential of harnessing riboflavin as an endogenous sensitizer for antibody-catalyzed oxidations and demonstrate a new approach for the development of an active vaccine for the treatment of nicotine addiction using in vivo catalytically active antibodies.
authors.affiliation: Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute 10550 North Torrey Pines Road La Jolla, CA 92037, USA.
authors.forename: Tobin J
authors.initials: TJ
authors.lastname: Dickerson
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D017151:Antibodies, Catalytic / Q000494:pharmacology*; D009538:Nicotine / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D012256:Riboflavin / Q000378:metabolism*
chemical_list: D017151:Antibodies, Catalytic; D009538:Nicotine; D012256:Riboflavin