Petty Sarah A, Decatur Sean M
Department of Chemistry, Mount Holyoke College, South Hadley, Massachusetts 01075, USA.
J Am Chem Soc. 2005 Oct 5;127(39):13488-9. doi: 10.1021/ja054663y.
Amyloidogenic deposits that accumulate in brain tissue with the progression of Alzheimer's disease contain large amounts of the amyloid beta-peptide. A small fragment of this peptide, comprising residues 16-22 (Abeta(16-22)), forms beta-sheets in isolation, which then aggregate into amyloid fibrils. Here, using isotope edited infrared spectroscopy to probe the secondary structure of the peptide with residue level specificity, we are able to show conclusively that the beta-sheets formed are antiparallel and, following an anneal cycle or prolonged incubation, are in register with the central residue (Phe19) in alignment across all strands. The alignment of strands proceeds via a rapid interchange from one sheet to another. This realignment of the peptide strands into a more favorable registry may have important implications for therapeutics since previous work has shown that well aligned beta-sheets form more stable amyloid fibrils.
随着阿尔茨海默病的进展，在脑组织中积累的淀粉样沉积物含有大量的β-淀粉样肽。该肽的一个小片段，由16-22位残基组成（Aβ(16-22)），单独形成β-折叠，然后聚集形成淀粉样纤维。在这里，我们使用同位素编辑红外光谱以残基水平特异性探测肽的二级结构，能够确凿地表明形成的β-折叠是反平行的，并且在退火循环或长时间孵育后，所有链上的中心残基（Phe19）对齐排列。链的对齐通过从一个折叠快速交换到另一个折叠进行。肽链重新排列成更有利的对齐方式可能对治疗具有重要意义，因为先前的研究表明排列良好的β-折叠会形成更稳定的淀粉样纤维。
