PNAS:小分子可稳定淀粉样蛋白生成免疫球蛋白轻链

2019-04-12 海北 MedSci原创

在Ig轻链(LC)淀粉样变性(AL)中,由每个患者中的单克隆浆细胞分泌的独特抗体LC蛋白错误折叠和/或聚集,这是导致器官变性的过程。

Ig轻链(LC)淀粉样变性(AL)中,由每个患者中的单克隆浆细胞分泌的独特抗体LC蛋白错误折叠和/或聚集,这是导致器官变性的过程。

为了给难以耐受现有化疗方案的心脏损伤的AL患者开发新的治疗方案,研究人员引入了全长LC的天然二聚体结构的小分子动力学稳定剂,其可以减缓或阻止其起源的淀粉样蛋白性级联反应。

研究人员使用蛋白酶偶联的基于荧光偏振的高通量筛选来鉴定动力学稳定LC的小分子。 

NMRX射线晶体学数据表明,利用在大多数AL患者中高度保守的可变结构域残基,所得小分子至少有一个结构家族结合在全长LC内的LC-LC二聚化界面。

经证实,在开始时停止淀粉样蛋白生成级联是改善有丝分裂后组织变性的潜在策略。


原始出处:

Morgan GJ et al. Stabilization of amyloidogenic immunoglobulin light chains by small molecules. PNAS, 2019; doi: 10.1073/pnas.1817567116.


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    2020-01-28 drwjr
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    2019-09-03 宋威
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    2019-08-21 xzw113
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