Raveendra Bindu L, Wu Hao, Baccala Roberto, Reddy M Muralidhar, Schilke Jessica, Bennett Jeffrey L, Theofilopoulos Argyrios N, Kodadek Thomas
Departments of Chemistry and Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
Chem Biol. 2013 Mar 21;20(3):351-9. doi: 10.1016/j.chembiol.2012.12.009.
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.
视神经脊髓炎(NMO)是一种中枢神经系统的自身免疫性炎症性疾病。在大多数NMO患者中,水通道蛋白4(AQP4)的自身抗体水平很高,被认为通过介导补体依赖性星形胶质细胞破坏来驱动病理过程。在此,我们应用最近开发的化学文库筛选技术,以鉴定一种能与NMO患者血清中的抗AQP4抗体结合的合成类肽。这一发现证实,在一种明确的人类疾病中,可以通过高通量筛选分离出与疾病相关抗体抗原结合位点的合成非天然配体。