Self-aggregation of a polyalanine octamer promoted by its C-terminal tyrosine and probed by a strongly enhanced vibrational circular dichroism signal.
Self-aggregation of a polyalanine octamer promoted by its C-terminal tyrosine and probed by a strongly enhanced vibrational circular dichroism signal.
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聚丙氨酸八聚体的自聚集由其 C 端酪氨酸促进，并通过强烈增强的振动圆二色性信号进行探测。
DOI：
10.1021/ja908324m
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发表时间：
2009
影响因子：
15
通讯作者：
Schweitzer-Stenner,Reinhard
中科院分区：
文献类型：
--
作者：
Measey,ThomasJ;Smith,KathrynB;Decatur,SeanM;Zhao,Liming;Yang,Guoliang;Schweitzer-Stenner,Reinhard
发现八残基丙氨酸寡肽 Ac-A4KA2Y-NH2(AKY8) 在肽浓度 > 10 mM 的酸化水溶液中室温孵育后可形成淀粉样蛋白样原纤维。原纤维溶液在酰胺 I' 带区域中表现出增强的振动圆二色性 (VCD) 对，该信号比该区域中的典型多肽/蛋白质信号大近 2 个数量级。原纤维溶液的 UV-CD 光谱显示 CD 位于与酪氨酸侧链吸收相关的区域。类似的肽 Ac-A4KA2-NH2(AK7) 由于缺乏末端酪氨酸残基，因此不会聚集。这些结果表明 C 端酪氨酸残基在稳定该肽的聚集状态方面发挥着关键作用。据推测，反平行排列的连续链的赖氨酸和酪氨酸侧链之间的相互作用（例如，阳离子-π相互作用）负责所产生的原纤维的稳定。这些结果提供了有关用于生物医学和生物技术应用的自组装寡肽的从头设计的考虑和见解，并强调了 VCD 作为探测淀粉样原纤维形成的工具的有用性。
The eight-residue alanine oligopeptide Ac-A4KA2Y-NH2(AKY8) was found to form amyloid-like fibrils upon incubation at room temperature in acidified aqueous solution at peptide concentrations >10 mM. The fibril solution exhibits an enhanced vibrational circular dichroism (VCD) couplet in the amide I′ band region that is nearly 2 orders of magnitude larger than typical polypeptide/protein signals in this region. The UV-CD spectrum of the fibril solution shows CD in the region associated with the tyrosine side chain absorption. A similar peptide, Ac-A4KA2-NH2(AK7), which lacks a terminal tyrosine residue, does not aggregate. These results suggest a pivotal role for the C-terminal tyrosine residue in stabilizing the aggregation state of this peptide. It is speculated that interactions between the lysine and tyrosine side chains of consecutive strands in an antiparallel arrangement (e.g., cation−π interactions) are responsible for the stabilization of the resulting fibrils. These results offer considerations and insight regarding the de novo design of self-assembling oligopeptides for biomedical and biotechnological applications and highlight the usefulness of VCD as a tool for probing amyloid fibril formation.