Li Jing, Chen Rui, Zhang Shasha, Ma Zhongjie, Luo Zhuoying, Gao Guanbin
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, No.122 Luoshi Road, Wuhan 430070, China.
School of Arts and Media, Wuhan Vocational College of Software and Engineering, No. 117 Guanggu Road, Wuhan 430205, China.
Nanomaterials (Basel). 2019 Mar 11;9(3):412. doi: 10.3390/nano9030412.
Protein/Peptide amyloidosis is the main cause of several diseases, such as neurodegenerative diseases. It has been widely acknowledged that the unnatural fibrillation of protein/peptides in vivo is significantly affected by the physical and chemical properties of multiscale biological membranes. For example, previous studies have proved that molecule chirality could greatly influence the misfolding, fibrillation and assembly of β-Amyloid peptides at the flat liquid-solid surface. However, how the nanoscale chirality influences this process remains unclear. Here we used gold nanoparticles (AuNPs, d = 4 ± 1 nm)-modified with -isobutyl-()-cysteine (()-NIBC) enantiomers-as a model to illustrate the chiral effect on the amylin fibrillation at nano-bio interface. We reported that both two chiral AuNPs could inhibit amylin fibrillation in a dosage-dependent manner but the inhibitory effect of -NIBC-AuNPs was more effective than that of -NIBC-AuNPs. In-situ real time circular dichroism (CD) spectra showed that -NIBC-AuNPs could inhibit the conformation transition process of amylin from random coils to α-helix, while -NIBC-AuNPs could only delay but not prevent the formation of α-helix; however, they could inhibit the further conformation transition process of amylin from α-helix to β-sheet. These results not only provide interesting insight for reconsidering the mechanism of peptides amyloidosis at the chiral interfaces provided by biological nanostructures in vivo but also would help us design therapeutic inhibitors for anti-amyloidosis targeting diverse neurodegenerative diseases.
蛋白质/肽淀粉样变性是多种疾病的主要病因，如神经退行性疾病。人们普遍认为，蛋白质/肽在体内的非自然纤维化受到多尺度生物膜物理和化学性质的显著影响。例如，先前的研究证明，分子手性可在平坦的液固表面极大地影响β-淀粉样肽的错误折叠、纤维化和组装。然而，纳米级手性如何影响这一过程仍不清楚。在这里，我们使用用（-）-异丁基-（-）-半胱氨酸（（-）-NIBC）对映体修饰的金纳米颗粒（AuNPs，d = 4 ± 1 nm）作为模型，来说明纳米生物界面上手性对胰淀素纤维化的影响。我们报道，两种手性AuNPs均能以剂量依赖的方式抑制胰淀素纤维化，但（-）-NIBC-AuNPs的抑制作用比（+）-NIBC-AuNPs更有效。原位实时圆二色性（CD）光谱表明，（-）-NIBC-AuNPs可抑制胰淀素从无规卷曲到α-螺旋的构象转变过程，而（+）-NIBC-AuNPs只能延迟但不能阻止α-螺旋的形成；然而，它们均可抑制胰淀素从α-螺旋到β-折叠的进一步构象转变过程。这些结果不仅为重新考虑体内生物纳米结构提供的手性界面上肽淀粉样变性的机制提供了有趣的见解，也将有助于我们设计针对多种神经退行性疾病的抗淀粉样变性治疗抑制剂。
