The Aβ 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater β-sheet forming and aggregation propensities in vitro than full-length Aβ
The Aβ 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater β-sheet forming and aggregation propensities in vitro than full-length Aβ
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DOI：
10.1021/bi990563r
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发表时间：
1999-08-17
期刊：
影响因子：
2.9
通讯作者：
Barrow, CJ
中科院分区：
文献类型：
--
作者：
He, WL;Barrow, CJ
从阿尔茨海默病患者脑的神经炎斑和血管壁分离的β已显示含有显著量的A β肽，其开始于焦谷氨酰残基形式的残基（3）Glu或（11）Glu（A β 3 pE和A β 11 pE）。为了研究这些N-末端修饰对A β生物物理性质的影响，合成了肽A β 1-40、A β 3 pE-40、A β 11 pE 40、A β 1-28、A β 3 pE-28和A β 11 pE-28。使用圆二色光谱，我们确定的焦谷氨酰含有肽形成β-折叠结构更容易比相应的全长A β肽，无论是在水溶液中，并在10%的十二烷基硫酸钠胶束。三氟乙醇光谱表明，相对β-折叠α-螺旋的稳定性较高的焦谷氨酰含肽。沉降实验表明，含有焦谷氨酰的肽具有比相应的全长肽更大的聚集倾向。A β 40和A β 28系列之间的比较表明，焦谷氨酰肽的更大的β-折叠形成和聚集倾向不仅仅是由于疏水性的增加。
A beta isolared from neuritic plaque and vascular walls of the brains of patients with Alzheimer's disease has been shown to contain significant quantities of A beta peptides which begin at residue (3)Glu or (11)Glu in the form of pyroglutamyl residues (A beta 3pE and A beta 11pE). To investigate the effects of these N-terminal modifications on the biophysical properties of A beta, peptides A beta 1-40, A beta 3pE-40, A beta 11pE40, A beta 1-28, A beta 3pE-28, and A beta 11pE-28 were synthesized. Using circular dichroism spectroscopy, we determined that the pyroglutamyl-containing peptides form beta-sheet structure more readily than the corresponding full-length A beta peptides, both in aqueous solutions and in 10% sodium dodecyl sulfate micelles. Trifluoroethanol spectra indicated that the relative beta-sheet to alpha-helical stability is higher for the pyroglutamyl-containing peptides. Sedimentation experiments show that the pyroglutamyl-containing peptides have greater aggregation propensities than the corresponding full-length peptides. Comparison between the A beta 40 and the A beta 28 series indicated that the greater beta-sheet forming and aggregation propensities of the pyroglutamyl peptides are not simply due to an increase in hydrophobicity.