title: Antibody-catalyzed anaerobic destruction of methamphetamine.
abstract: Methamphetamine [(+)-2] abuse has emerged as a fast-rising global epidemic, with immunopharmacotherapeutic approaches being sought for its treatment. Herein, we report the generation and characterization of a monoclonal antibody, YX1-40H10, that catalyzes the photooxidation of (+)-2 into the nonpsychoactive compound benzaldehyde (14) under anaerobic conditions in the presence of riboflavin (6). Studies have revealed that the antibody facilitates the conversion of (+)-2 into 14 by binding the triplet photoexcited state of 6 in proximity to (+)-2. The antibody binds riboflavin (K(d) = 180 muM), although this was not programmed into hapten design, and the YX1-40H10-catalyzed reaction is inhibited by molecular oxygen via the presumed quenching of the photoexcited triplet state of 6. Given that this reaction is another highlight in the processing of reactive intermediates by antibodies, we speculate that this process may have future significance in vivo with programmed immunoglobulins that use flavins as cofactors to destroy selectable molecular targets under hypoxic or even anoxic conditions.
authors.affiliation: Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hixon
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Laura A
authors.initials: LA
authors.lastname: McAllister
authors.forename: Anita D
authors.initials: AD
authors.lastname: Wentworth
authors.forename: Paul
authors.initials: P
authors.lastname: Wentworth
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000818:Animals; D017151:Antibodies, Catalytic / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002384:Catalysis; D000860:Hypoxia; D007136:Immunoglobulins / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods; D007700:Kinetics; D008027:Light; D008694:Methamphetamine / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008956:Models, Chemical; D010100:Oxygen / Q000737:chemistry; D012256:Riboflavin / Q000737:chemistry; D014612:Vaccines / Q000737:chemistry
chemical_list: D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D014612:Vaccines; D008694:Methamphetamine; D010100:Oxygen; D012256:Riboflavin