Antibody-catalyzed anaerobic destruction of methamphetamine
- Yang Xu†,‡,
- Mark S. Hixon†,‡,
- Noboru Yamamoto†,‡,§,
- Laura A. McAllister†,‡,
- Anita D. Wentworth†,
- Paul Wentworth, Jr.†,‡,¶,‖, and
- Kim D. Janda†,‡,§,‖,††
- Departments of †Chemistry and
- ††Immunology,
- ‡The Skaggs Institute for Chemical Biology, and
- §The Worm Institute for Research and Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and
- ¶The Scripps–Oxford Laboratory, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom
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Communicated by Richard A. Lerner, The Scripps Research Institute, La Jolla, CA, December 18, 2006 (received for review December 2, 2006)
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 μM), 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.
Footnotes
- ‖To whom correspondence may be addressed. E-mail: paulw{at}scripps.edu or kdjanda{at}scripps.edu
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Author contributions: A.D.W., P.W., and K.D.J. designed research; Y.X., N.Y., and L.A.M. performed research; M.S.H., A.D.W., P.W., and K.D.J. analyzed data; and Y.X., P.W., and K.D.J. wrote the paper.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0611094104/DC1.
- Abbreviation:
- DNPH,
- dinitrophenylhydrazine.
- © 2007 by The National Academy of Sciences of the USA
