Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, 76019, USA.
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, 76019, USA.
Anal Chim Acta. 2021 Jun 8;1163:338506. doi: 10.1016/j.aca.2021.338506. Epub 2021 Apr 11.
Extracellular deposition of amyloid beta (Aβ) peptides are a hallmark of Alzheimer's disease. The isomerization and epimerization of Aβ peptides have been linked to the enhanced deposition of Aβ plaques. Therefore, considerable effort has been expended to create effective methods to distinguish such aberrant Aβ peptides from normal Aβ peptides. Herein, we have developed chromatographic retention U-shaped curves to investigate the hydrophobicity of Aβ 1-38, 1-40, 1-42 and fourteen aberrant Aβ 1-42 peptides. Using this information, we developed the first selective and comprehensive method that can easily detect both aberrant and normal Aβ peptides simultaneously using high performance liquid chromatography-mass spectrometry (HPLC-MS). We show for the first time that D-Ser modifications to Aβ cause the peptide to be more hydrophilic, as does D-Asp and L/D-iso-Asp.
细胞外淀粉样蛋白β (Aβ) 肽的沉积是阿尔茨海默病的一个标志。Aβ 肽的异构化和差向异构化与 Aβ 斑块的沉积增强有关。因此，人们付出了相当大的努力来创造有效的方法来区分这种异常的 Aβ 肽与正常的 Aβ 肽。在这里，我们开发了色谱保留 U 形曲线来研究 Aβ 1-38、1-40、1-42 和 14 种异常 Aβ 1-42 肽的疏水性。利用这些信息，我们开发了第一种选择性和全面的方法，可以使用高效液相色谱-质谱联用技术 (HPLC-MS) 轻松同时检测异常和正常 Aβ 肽。我们首次表明，Aβ 中的 D-丝氨酸修饰使肽更亲水，D-天冬氨酸和 L/D-异天冬氨酸也是如此。
