title: Synthesis and immunological effects of heroin vaccines.
abstract: Three haptens have been synthesized with linkers for attachment to carrier macromolecules at either the piperidino-nitrogen or via an introduced 3-amino group. Two of the haptens, with a 2-oxopropyl functionality at either C6, or at both the C3 and C6 positions on the 4,5-epoxymorphinan framework, as well as the third hapten (DiAmHap) with diamido moieties at both the C3 and C6 positions, should be much more stable in solution, or in vivo in a vaccine, than a hapten with an ester in one of those positions, as found in many heroin-based haptens. A "classical" opioid synthetic scheme enabled the formation of a 3-amino-4,5-epoxymorphinan which could not be obtained using palladium chemistry. Our vaccines are aimed at the reduction of the abuse of heroin and, as well, at the reduction of the effects of its predominant metabolites, 6-acetylmorphine and morphine. One of the haptens, DiAmHap, has given interesting results in a heroin vaccine and is clearly more suited for the purpose than the other two haptens.
authors.affiliation: Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, 9800 Medical Center Drive, Bethesda, MD 20892, USA. kenner.rice@nih.gov.
authors.forename: Fuying
authors.initials: F
authors.lastname: Li
authors.forename: Kejun
authors.initials: K
authors.lastname: Cheng
authors.forename: Joshua F G
authors.initials: JF
authors.lastname: Antoline
authors.forename: Malliga R
authors.initials: MR
authors.lastname: Iyer
authors.forename: Gary R
authors.initials: GR
authors.lastname: Matyas
authors.forename: Oscar B
authors.initials: OB
authors.lastname: Torres
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jalah
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Beck
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
authors.forename: Damon A
authors.initials: DA
authors.lastname: Parrish
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Deschamps
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Jacobson
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
mesh_terms: D000818:Animals; D005260:Female; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D003932:Heroin / Q000737:chemistry / Q000276:immunology*; D006556:Heroin Dependence / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008968:Molecular Conformation; D014612:Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*
chemical_list: D006241:Haptens; D046911:Macromolecular Substances; D014612:Vaccines; D003932:Heroin