Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC, 172-27, USA.
Angew Chem Int Ed Engl. 2018 May 22;57(21):6212-6215. doi: 10.1002/anie.201802269. Epub 2018 Apr 25.
Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death, with average survival times of two to five years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a phenomenon influenced by point mutations spanning the protein. Herein, we used an epitope-specific high-throughput screen to identify a peptide ligand that stabilizes the SOD1 native conformation and accelerates its folding by a factor of 2.5. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics.
肌萎缩侧索硬化症，又称卢伽雷氏病，其特征是运动神经元死亡，平均存活时间为 2 到 5 年。这种疾病的一个原因是超氧化物歧化酶 1（SOD1）的错误折叠，这一现象受跨越蛋白质的点突变影响。在此，我们使用表位特异性高通量筛选鉴定了一种肽配体，它能稳定 SOD1 的天然构象，并将其折叠速度提高 2.5 倍。该策略可能对蛋白质能量景观的基础研究以及设计新型治疗药物都有帮助。
