title: The synthesis of haptens and their use for the development of monoclonal antibodies for treating methamphetamine abuse.
abstract: In addition to addiction, the repeated use of (+)-methamphetamine [(+)-METH], (+)-amphetamine [(+)-AMP], or (+/-)-3,4-methylenedioxymethamphetamine ((+/-)-MDMA, commonly called ecstasy) can lead to life-threatening medical problems including cardiovascular injury, severe depression, and psychosis. Currently, there are no specific pharmacotherapies to treat these medical problems. In this study, we report the design and synthesis of two haptens, (S)-(+)-3-(9-carboxynonyloxy)methamphetamine (3a, (+)-METH MO10) and (S)-(+)-3-(5-carboxypentyloxy)methamphetamine (3b, (+)-METH MO6), and their use in generating high affinity (low K(D) value) monoclonal antibodies (mAbs) against (+)-METH, (+)-AMP, and/or (+)-MDMA. On the basis of results from the determination of mAb K(D) values and ligand specificity, the mAbs generated from hapten 3a showed the greatest promise for generating active and passive immunotherapies for treating overdose or addiction from (+)-METH-like stimulants.
authors.affiliation: Center for Organic and Medicinal Chemistry, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, North Carolina 27709, USA. fic@rti.org
authors.forename: F Ivy
authors.initials: FI
authors.lastname: Carroll
authors.forename: Philip
authors.initials: P
authors.lastname: Abraham
authors.forename: Paul K
authors.initials: PK
authors.lastname: Gong
authors.forename: Ramakrishna R
authors.initials: RR
authors.lastname: Pidaparthi
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Blough
authors.forename: Yingni
authors.initials: Y
authors.lastname: Che
authors.forename: Amber
authors.initials: A
authors.lastname: Hampton
authors.forename: Melinda
authors.initials: M
authors.lastname: Gunnell
authors.forename: Jackson O
authors.initials: JO
authors.lastname: Lay
authors.forename: Eric C
authors.initials: EC
authors.lastname: Peterson
authors.forename: S Michael
authors.initials: SM
authors.lastname: Owens
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D055808:Drug Discovery; D005260:Female; D006241:Haptens / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D007114:Immunization; D008694:Methamphetamine; D051379:Mice; D010047:Ovalbumin / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D019966:Substance-Related Disorders / Q000276:immunology*; D013379:Substrate Specificity
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D006241:Haptens; D008694:Methamphetamine; D010047:Ovalbumin