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Positional linker effects in haptens for cocaine immunopharmacotherapy

Academic Article
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Overview

authors

  • Ino, A.
  • Dickerson, Tobin
  • Janda, Kim

publication date

  • August 2007

journal

  • Bioorganic & Medicinal Chemistry Letters  Journal

abstract

  • Cocaine use remains a serious problem, despite intensive efforts to curb abuse. Given the lack of effective pharmacotherapeutics for the treatment of cocaine addiction, research groups have targeted immunopharmacotherapy in which the drug user's immune system is trained to recognize and remove cocaine prior to entry into the central nervous system. Antibody cocaine esterases and simple binders have been procured, however, rates and/or affinities still need improvement before clinical trials are warranted. Herein, we report the synthesis and testing of two new haptens for the procurement of cocaine binding antibodies and cocaine esterase catalytic antibodies. Central in the design of these haptens was the placement of the linker functionality distal from the anticipated cocaine epitopes in an attempt to bury the hapten deep within an antibody combining site to gain possible entropic and enthalpic advantages.

subject areas

  • Cocaine-Related Disorders
  • Crystallography, X-Ray
  • Enzyme-Linked Immunosorbent Assay
  • Haptens
  • Humans
  • Immunotherapy
  • Models, Molecular
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Research

keywords

  • cocaine
  • drugs of abuse
  • immunopharmacotherapy
  • transition state analog
  • vaccine
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Identity

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2007.05.032

PubMed ID

  • 17531484
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Additional Document Info

start page

  • 4280

end page

  • 4283

volume

  • 17

issue

  • 15

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