Positional linker effects in haptens for cocaine immunopharmacotherapy

Bioorg Med Chem Lett. 2007 Aug 1;17(15):4280-3. doi: 10.1016/j.bmcl.2007.05.032. Epub 2007 May 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cocaine-Related Disorders / drug therapy*
  • Crystallography, X-Ray
  • Enzyme-Linked Immunosorbent Assay
  • Haptens / chemistry
  • Haptens / therapeutic use*
  • Humans
  • Immunotherapy*
  • Models, Molecular

Substances

  • Haptens