Discovery of peptoid ligands for anti-aquaporin 4 antibodies

Chem Biol. 2013 Mar 21;20(3):351-9. doi: 10.1016/j.chembiol.2012.12.009.

Abstract

Neuromyelitis optica (NMO) is an autoimmune inflammatory disorder of the central nervous system. In most NMO patients, autoantibodies to the water channel protein Aquaporin 4 (AQP4) are present at high levels and are thought to drive pathology by mediating complement-dependent destruction of astrocytes. Here, we apply recently developed chemical library screening technology to identify a synthetic peptoid that binds anti-AQP4 antibodies in the serum of NMO patients. This finding validates, in a well-defined human disease, that synthetic, unnatural ligands for the antigen-binding site of a disease-linked antibody can be isolated by high-throughput screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnosis
  • Antibodies / blood
  • Antibodies / immunology*
  • Antibodies / metabolism*
  • Aquaporin 4 / immunology*
  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Humans
  • Ligands
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / diagnosis
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / diagnosis
  • Narcolepsy / blood
  • Narcolepsy / diagnosis
  • Neuromyelitis Optica / blood
  • Neuromyelitis Optica / diagnosis
  • Peptoids / metabolism*
  • Small Molecule Libraries / metabolism

Substances

  • Antibodies
  • Aquaporin 4
  • Ligands
  • Peptoids
  • Small Molecule Libraries