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Probing active cocaine vaccination performance through catalytic and noncatalytic hapten design

Academic Article
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Overview

authors

  • Cai, X.
  • Whitfield, T.
  • Hixon, M. S.
  • Grant, Y.
  • Koob, George
  • Janda, Kim

publication date

  • May 2013

journal

  • Journal of Medicinal Chemistry  Journal

abstract

  • Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complementary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH (keyhole limpet hemocyannin) was found to elicit persistent high-titer, cocaine-specific antibodies and blunt cocaine-induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges, the vaccine's protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse.

subject areas

  • Animals
  • Antibodies
  • Antibody Specificity
  • Biocatalysis
  • Cocaine
  • Drug Design
  • Haptens
  • Immunoconjugates
  • Kinetics
  • Locomotion
  • Mice
  • Vaccination
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Identity

PubMed Central ID

  • PMC3691275

International Standard Serial Number (ISSN)

  • 1520-4804 (Electronic) 0022-2623 (Linking)

Digital Object Identifier (DOI)

  • 10.1021/jm400228w

PubMed ID

  • 23627877
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Additional Document Info

start page

  • 3701

end page

  • 3709

volume

  • 56

issue

  • 9

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