Racemization of the amyloidal β Asp1 residue blocks the acceleration of fibril formation caused by racemization of the ASP23 residue
Racemization of the amyloidal β Asp1 residue blocks the acceleration of fibril formation caused by racemization of the ASP23 residue
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DOI：
10.1016/j.bbrc.2007.10.014
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发表时间：
2007-12-21
影响因子：
3.1
通讯作者：
Utsunomiya-Tate, Naoko
中科院分区：
文献类型：
--
作者：
Sakai-Kato, Kumiko;Naito, Megumi;Utsunomiya-Tate, Naoko
从神经炎斑块的淀粉样蛋白核心提取的淀粉样蛋白在其Asp残基处被相当程度地外消旋化。为了评估D-Asp对淀粉样蛋白β（1-42）构象和淀粉样蛋白原纤维形成起始的影响，我们使用野生型淀粉样蛋白β（1-42）和类似物，其中D-Asp在残基1、7、23和这些残基的所有组合处取代L-Asp。D-天冬氨酸可增强淀粉样原纤维的形成（23）;调节N-末端1位的天冬氨酸手性可阻断这种增强作用，而调节7位可增强这种增强作用。了解这种手性修饰可能有助于开发淀粉样原纤维形成的有效抑制剂。(C)2007年爱思唯尔公司All rights reserved.
Amyloid proteins extracted from the amyloid cores of neuritic plaques are considerably racemized at their Asp residues. To assess the impact Of D-Asp on amyloid beta(1-42) conformation and on initiation of amyloid fibril formation, we used wild-type amyloid beta(1-42) and analogs in which D-Asp was substituted for L-Asp at residues 1, 7, 23, and all combinations of these residues. Amyloid fibril formation was enhanced by D-ASP(23); modulation of Asp chirality at N-terminal position 1 blocked this enhancement and modulation at position 7 augmented it. Knowledge of such chirality modifications may help to develop potent inhibitors of amyloid fibril formation. (C) 2007 Elsevier Inc. All rights reserved.