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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.

SUBMITTER: Xu Y 

PROVIDER: S-EPMC1820643 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Antibody-catalyzed anaerobic destruction of methamphetamine.

Xu Yang Y   Hixon Mark S MS   Yamamoto Noboru N   McAllister Laura A LA   Wentworth Anita D AD   Wentworth Paul P   Janda Kim D KD  

Proceedings of the National Academy of Sciences of the United States of America 20070228 10


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 tri  ...[more]

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