Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
J Phys Chem B. 2011 Sep 22;115(37):11010-6. doi: 10.1021/jp206271e. Epub 2011 Aug 29.
Amyloid fibrils, which are often associated with certain degenerative disorders, reveal a number of intriguing spectral properties. However, the relationship between the structure of fibrils and their optical traits remains poorly understood. Poly(L-glutamic) acid is a model polypeptide shown recently to form amyloid-like fibrils with an atypical infrared amide I' band at 1595 cm(-1), which has been attributed to the presence of bifurcated hydrogen bonds coupling C═O and N-D groups of the main chains to glutamate side chains. Here we show that this unusual amide I' band is observed only for fibrils grown from pure enantiomers of the polypeptide, whereas fibrils precipitating from equimolar mixtures of poly(L-glutamic) and poly(D-glutamic) acids have amide I' bands at 1684 and 1612 cm(-1), which are indicative of a typical intermolecular antiparallel β-sheet. Pure enantiomers of polyglutamic acid form spirally twisted superstructures whose handedness is correlated to the amino acid chirality, while fibrils prepared from the racemate do not form scanning electron microscopy (SEM)-detectable mesoscopically ordered structures. Vibrational circular dichroism (VCD) spectra of β-aggregates prepared from mixtures of all L- or D-polyglutamic acid in varying ratios indicate that the enhancement of VCD intensity correlates with the presence of the twisted superstructures. Our results demonstrate that both IR absorption and enhanced VCD are sensitive to subtle packing defects taking place within the compact structure of amyloid fibrils.
淀粉样纤维通常与某些退行性疾病有关，显示出许多有趣的光谱特性。然而，纤维的结构与其光学性质之间的关系仍未得到很好的理解。聚（L-谷氨酸）酸是一种最近被证明能形成类似淀粉样纤维的模型多肽，其在 1595cm(-1)处有一个非典型的红外酰胺 I'带，这归因于存在分叉氢键，将主链的 C═O 和 N-D 基团与谷氨酸侧链偶联。在这里，我们表明，只有从多肽的纯对映体中生长的纤维才会观察到这种不寻常的酰胺 I'带，而从等摩尔比的聚（L-谷氨酸）和聚（D-谷氨酸）酸的混合物中沉淀出的纤维具有在 1684 和 1612cm(-1)处的酰胺 I'带，这表明存在典型的分子间反平行 β-折叠。聚谷氨酸的纯对映体形成螺旋扭曲的超结构，其手性与氨基酸的手性相关，而由外消旋体制备的纤维则不会形成可通过扫描电子显微镜（SEM）检测到的介观有序结构。从所有 L-或 D-聚谷氨酸以不同比例混合制备的 β-聚集体的振动圆二色性（VCD）谱表明，VCD 强度的增强与扭曲超结构的存在相关。我们的结果表明，IR 吸收和增强的 VCD 都对发生在淀粉样纤维紧凑结构内的微妙堆积缺陷敏感。
