Development of Tetramethylenedisulfotetramine (TETS) Hapten Library: Synthesis, Electrophysiological Studies, and Immune Response in Rabbits

Chemistry. 2017 Jun 22;23(35):8466-8472. doi: 10.1002/chem.201700783. Epub 2017 May 30.

Abstract

There is a need for fast detection methods for the banned rodenticide tetramethylenedisulfotetramine (TETS), a highly potent blocker of the γ-aminobutyric acid (GABAA ) receptors. General synthetic approach toward two groups of analogues was developed. Screening of the resulting library of compounds by FLIPR or whole-cell voltage-clamp revealed that, despite the structural differences, some of the TETS analogues retained GABAA receptor inhibition; however, their potency was an order of magnitude lower. Antibodies raised in rabbits against some of the TETS analogues conjugated to protein recognized free TETS and will be used for the development of an immunoassay for TETS.

Keywords: GABA; antibodies; cage convulsants; neurotoxicity; poly-heterocycles; tetramine.

MeSH terms

  • Animals
  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / pharmacology
  • Drug Evaluation, Preclinical / methods
  • Electrophysiological Phenomena / physiology
  • Haptens / chemistry*
  • Humans
  • Immunoassay / methods
  • Inhibitory Concentration 50
  • Molecular Structure
  • Neurons
  • Rabbits
  • Receptors, GABA-A / metabolism*
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / pharmacology
  • Structure-Activity Relationship

Substances

  • Bridged-Ring Compounds
  • Haptens
  • Receptors, GABA-A
  • Small Molecule Libraries
  • tetramethylenedisulfotetramine