title: Discovery of peptoid ligands for anti-aquaporin 4 antibodies.
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.
authors.affiliation: Departments of Chemistry and Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Bindu L
authors.initials: BL
authors.lastname: Raveendra
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Roberto
authors.initials: R
authors.lastname: Baccala
authors.forename: M Muralidhar
authors.initials: MM
authors.lastname: Reddy
authors.forename: Jessica
authors.initials: J
authors.lastname: Schilke
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bennett
authors.forename: Argyrios N
authors.initials: AN
authors.lastname: Theofilopoulos
authors.forename: Thomas
authors.initials: T
authors.lastname: Kodadek
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis; D000906:Antibodies / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D051401:Aquaporin 4 / Q000276:immunology*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000175:diagnosis; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis; D009290:Narcolepsy / Q000097:blood / Q000175:diagnosis; D009471:Neuromyelitis Optica / Q000097:blood / Q000175:diagnosis; D034444:Peptoids / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000378:metabolism
chemical_list: D000906:Antibodies; D051401:Aquaporin 4; D008024:Ligands; D034444:Peptoids; D054852:Small Molecule Libraries