Β-AMYLOID(1-9)肽 | 147529-30-4

• 物质功能分类: 生物化工 - 多肽
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: Β-AMYLOID(1-9)肽
• 中文别名: Β-AMYLOID (1-9)肽
• 英文名称: H₂N-AspAlaGluPheArgHisAspSerGly-NH₂
• 英文别名: H₂N-DAEFRHDSG-NH₂；Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly；DAEFRHDSG；beta-Amyloid (1-9)；(4S)-4-[[(2S)-2-[[(2S)-2-amino-3-carboxypropanoyl]amino]propanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-(carboxymethylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 147529-30-4
• 化学式: C₄₂H₆₀N₁₄O₁₇
• 分子量: 1033.02
• InChiKey: BRRKPUCEVBBGNV-WVQSQKPFSA-N

物化性质

• 密度：
  1.60±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  -8.6
• 重原子数：
  73
• 可旋转键数：
  33
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  521
• 氢给体数：
  17
• 氢受体数：
  20

制备方法与用途

概述

β-AMYLOID(1-9) 肽是由淀粉样前体蛋白（APP）经 β- 和 γ-分泌酶的蛋白水解作用产生的含有 1～9 个氨基酸的多肽。

用途

β-AMYLOID(1-9) 肽可用于研究高血压性脑白质损害大鼠的认知功能减退及脑内 β-淀粉样蛋白沉积。

生物活性

β-Amyloid (1-9) 是 β- 淀粉样蛋白的 N 端片段，由氨基酸残基 1 到 9 组成。它含有 B 细胞表位，但不包括 T 细胞表位。在全长阿尔茨海默病 β-淀粉样肽（1-40）中，1 到 9 的缺失不会阻止其形成淀粉样纤维或消除纤维多态性。

反应信息

• 作为反应物：
  描述：

  Β-AMYLOID(1-9)肽 、 丙酮醛 以 aq. phosphate buffer 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Glycation of Lys-16 and Arg-5 in amyloid-β and the presence of Cu2+ play a major role in the oxidative stress mechanism of Alzheimer’s disease

  摘要：

  Extensive research has linked the amyloid-beta (A beta) peptide to neurological dysfunction in Alzheimer's disease (AD). Insoluble A beta plaques in the AD patient brain contain high concentrations of advanced glycation end-products (AGEs) as well as transition metal ions. This research elucidated the roles of A beta, sugars, and Cu2+ in the oxidative stress mechanism of AD at the molecular level. Mass spectral (MS) analysis of the reactions of A beta with two representative sugars, ribose-5-phosphate (R5P) and methylglyoxal (MG), revealed Lys-16 and Arg-5 as the primary glycation sites. Quantitative analysis of superoxide production by a cyt c assay showed that Lys-16 generated four times as much as Arg-5. Lys-16 and Arg-5 in A beta(1-40) are both adjacent to histidine residues, which are suggested to catalyze glycation. Additionally, Lys-16 is close to the central hydrophobic core (Leu-17-Ala-21) and to His-13, both of which are known to lower the pKa of the residue, leading to increased deprotonation of the amine and an enhanced glycation reactivity compared to Arg-5. Gel electrophoresis results indicated that all three components of AD plaques-A beta(1-40), sugars, and Cu2+-are necessary for DNA damage. It is concluded that the glycation of A beta(1-40) with sugars generates significant amounts of , owing to the rapid glycation of Lys-16 and Arg-5. In the presence of Cu2+, converts to hydroxyl radical (HO center dot), the source of oxidative stress in AD.

  DOI：

  10.1007/s00775-017-1497-5
• 作为产物：
  描述：

  Fmoc-甘氨酸 、 Fmoc-L-丙氨酸 、 Fmoc-L-苯丙氨酸 、 FMOC-O-叔丁基-L-丝氨酸 、 Fmoc-L-天冬氨酸 beta-叔丁酯 、 Fmoc-O-叔丁基-L-谷氨酸 、 N-Fmoc-N'-三苯甲基-L-组氨酸 、 Fmoc-Pbf-L-精氨酸 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.05h， 生成 Β-AMYLOID(1-9)肽
  参考文献：
  名称：

  淀粉样β及其衍生物的N端九肽片段的铜（II），镍（II）和锌（II）配合物

  摘要：

  淀粉样βAβ （1–9）（NH 2 -DAEFRHDSG-NH 2）及其两个衍生物的非肽片段的铜（II），镍（II）和锌（II）配合物及其两个衍生物：NH 2 -DAAAAHAAA-NH 2和NH 2 -DAAAAAHAA-NH 2已经通过电位，紫外可见和CD光谱法进行了研究。结果揭示了肽的氨基末端在铜（II）和镍（II）结合中的主要作用。在含铜（II）的体系中也可能形成双核配合物，但在生理相关的pH范围内，只有氨基末端的前六个氨基酸参与金属结合。两种丙氨酸突变肽的配位化学与天然九肽的配位化学几乎相同，但突变体的铜（II）配合物的热力学稳定性显着降低。这种差异可能来自天然肽中存在的Asp，Glu，Ser和Arg残基的极性侧链的次级相互作用。而且，

  DOI：

  10.1016/j.jinorgbio.2014.06.001

文献信息

• Copper(II), nickel(II) and zinc(II) complexes of the N-terminal nonapeptide fragment of amyloid-β and its derivatives
  作者：Ágnes Grenács、Imre Sóvágó

  DOI：10.1016/j.jinorgbio.2014.06.001

  日期：2014.10

  Copper(II), nickel(II) and zinc(II) complexes of the nonapeptide fragment of amyloid-β Aβ(1–9) (NH2-DAEFRHDSG-NH2) and its two derivatives: NH2-DAAAAHAAA-NH2 and NH2-DAAAAAHAA-NH2 have been studied by potentiometric, UV–visible and CD spectroscopic methods. The results reveal the primary role of the amino terminus of peptides in copper(II) and nickel(II) binding. The formation of dinuclear complexes

  淀粉样βAβ （1–9）（NH 2 -DAEFRHDSG-NH 2）及其两个衍生物的非肽片段的铜（II），镍（II）和锌（II）配合物及其两个衍生物：NH 2 -DAAAAHAAA-NH 2和NH 2 -DAAAAAHAA-NH 2已经通过电位，紫外可见和CD光谱法进行了研究。结果揭示了肽的氨基末端在铜（II）和镍（II）结合中的主要作用。在含铜（II）的体系中也可能形成双核配合物，但在生理相关的pH范围内，只有氨基末端的前六个氨基酸参与金属结合。两种丙氨酸突变肽的配位化学与天然九肽的配位化学几乎相同，但突变体的铜（II）配合物的热力学稳定性显着降低。这种差异可能来自天然肽中存在的Asp，Glu，Ser和Arg残基的极性侧链的次级相互作用。而且，
• Glycation of Lys-16 and Arg-5 in amyloid-β and the presence of Cu2+ play a major role in the oxidative stress mechanism of Alzheimer’s disease
  作者：Sebastian M. Fica-Contreras、Sydney O. Shuster、Nathaniel D. Durfee、Gregory J. K. Bowe、Nathaniel J. Henning、Staci A. Hill、Geoffrey D. Vrla、David R. Stillman、Kelly M. Suralik、Roger K. Sandwick、Sunhee Choi

  DOI：10.1007/s00775-017-1497-5

  日期：2017.12

  Extensive research has linked the amyloid-beta (A beta) peptide to neurological dysfunction in Alzheimer's disease (AD). Insoluble A beta plaques in the AD patient brain contain high concentrations of advanced glycation end-products (AGEs) as well as transition metal ions. This research elucidated the roles of A beta, sugars, and Cu2+ in the oxidative stress mechanism of AD at the molecular level. Mass spectral (MS) analysis of the reactions of A beta with two representative sugars, ribose-5-phosphate (R5P) and methylglyoxal (MG), revealed Lys-16 and Arg-5 as the primary glycation sites. Quantitative analysis of superoxide production by a cyt c assay showed that Lys-16 generated four times as much as Arg-5. Lys-16 and Arg-5 in A beta(1-40) are both adjacent to histidine residues, which are suggested to catalyze glycation. Additionally, Lys-16 is close to the central hydrophobic core (Leu-17-Ala-21) and to His-13, both of which are known to lower the pKa of the residue, leading to increased deprotonation of the amine and an enhanced glycation reactivity compared to Arg-5. Gel electrophoresis results indicated that all three components of AD plaques-A beta(1-40), sugars, and Cu2+-are necessary for DNA damage. It is concluded that the glycation of A beta(1-40) with sugars generates significant amounts of , owing to the rapid glycation of Lys-16 and Arg-5. In the presence of Cu2+, converts to hydroxyl radical (HO center dot), the source of oxidative stress in AD.