Department of Chemistry, University of Illinois at Chicago , 845 W. Taylor Street (m/c111), Chicago, Illinois 60607-7061, United States.
Langmuir. 2016 May 10;32(18):4653-61. doi: 10.1021/acs.langmuir.6b00077. Epub 2016 Apr 29.
Poly(glutamic acid) at low pH self-assembles after incubation at higher temperature into fibrils composed of antiparallel sheets that are stacked in a β2-type structure whose amide carbonyls have bifurcated H-bonds involving the side chains from the next sheet. Oligomers of Glu can also form such structures, and isotope labeling has provided insight into their out-of-register antiparallel structure [ Biomacromolecules 2013 , 14 , 3880 - 3891 ]. In this paper we report IR and VCD spectra and transmission electron micrograph (TEM) images for a series of alternately sequenced oligomers, Lys-(Aaa-Glu)5-Lys-NH2, where Aaa was varied over a variety of polar, aliphatic, or aromatic residues. Their spectral and TEM data show that these oligopeptides self-assemble into different structures, both local and morphological, that are dependent on both the nature of the Aaa side chains and growth conditions employed. Such alternate peptides substituted with small or polar residues, Ala and Thr, do not yield fibrils; but with β-branched aliphatic residues, Val and Ile, that could potentially pack with Glu side chains, these oligopeptides do show evidence of β2-stacking. By contrast, for Leu, with longer side chains, only β1-stacking is seen while with even larger Phe side chains, either β-form can be detected separately, depending on preparation conditions. These structures are dependent on high temperature incubation after reducing the pH and in some cases after sonication of initial fibril forms and reincubation. Some of these fibrillar peptides, but not all, show enhanced VCD, which can offer evidence for formation of long, multistrand, often twisted structures. Substitution of Glu with residues having selected side chains yields a variety of morphologies, leading to both β1- and β2-structures, that overall suggests two different packing modes for the hydrophobic side chains depending on size and type.
聚谷氨酸在较低 pH 值下自组装，然后在较高温度下孵育形成由反平行片层组成的纤维，这些片层以 β2 型结构堆叠，其酰胺羰基具有分叉的 H 键，涉及来自下一个片层的侧链。Glu 的低聚物也可以形成这种结构，同位素标记提供了对其非注册反平行结构的深入了解 [Biomacromolecules 2013, 14, 3880-3891]。在本文中，我们报告了一系列交替序列低聚物 Lys-(Aaa-Glu)5-Lys-NH2 的红外 (IR) 和圆二色 (VCD) 光谱和透射电子显微镜 (TEM) 图像，其中 Aaa 变化范围广泛，包括极性、脂肪族或芳香族残基。它们的光谱和 TEM 数据表明，这些低聚肽自组装成不同的结构，既有局部结构又有形态结构，这取决于 Aaa 侧链的性质和使用的生长条件。用小的或极性残基 Ala 和 Thr 取代的这些交替肽不产生纤维；但是用β-支链脂肪族残基 Val 和 Ile，它们有可能与 Glu 侧链结合，这些低聚肽确实显示出β2-堆积的证据。相比之下，对于具有较长侧链的 Leu，只观察到β1-堆积，而对于更大的 Phe 侧链，可以根据制备条件分别检测到β 形式。这些结构依赖于降低 pH 值后高温孵育，在某些情况下还依赖于初始纤维形式的超声处理和再孵育。这些纤维状肽中的一些，但不是全部，显示出增强的 VCD，这可以提供形成长的、多股的、通常扭曲的结构的证据。用具有选定侧链的残基取代 Glu 会产生多种形态，导致形成β1-和β2-结构，总体上表明疏水侧链有两种不同的堆积模式，这取决于大小和类型。
