Using Molecular Tweezers to Remodel Abnormal Protein Self-Assembly and Inhibit the Toxicity of Amyloidogenic Proteins.
Using Molecular Tweezers to Remodel Abnormal Protein Self-Assembly and Inhibit the Toxicity of Amyloidogenic Proteins.
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DOI：
10.1007/978-1-4939-7811-3_24
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Bitan G
中科院分区：
文献类型：
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作者：
Malik R;Di J;Nair G;Attar A;Taylor K;Teng E;Klärner FG;Schrader T;Bitan G
分子镊子 (MT) 是异常蛋白质自组装的广谱抑制剂，通过选择性结合赖氨酸和精氨酸残基发挥作用。通过这种独特的作用机制，MT 可抑制有毒低聚物和聚集体的形成。它们的功效和安全性已在体外、细胞培养和动物模型中得到证实。在这里，我们讨论 MT 在各种体外和体内系统中的应用、实验细节、其使用范围以及该方法的局限性。我们还考虑在动物模型中施用 MT 的方法，以测量蛋白质病中的功效、药代动力学和药效学参数。
Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein self-assembly, which act by binding selectively to lysine and arginine residues. Through this unique mechanism of action, MTs inhibit formation of toxic oligomers and aggregates. Their efficacy and safety have been demonstrated in vitro, in cell culture, and in animal models. Here, we discuss the application of MTs in diverse in vitro and in vivo systems, the experimental details, the scope of their use, and the limitations of the approach. We also consider methods for administration of MTs in animal models to measure efficacy, pharmacokinetic, and pharmacodynamic parameters in proteinopathies.