Kang Juhye, Nam Jung Seung, Lee Hyuck Jin, Nam Geewoo, Rhee Hyun-Woo, Kwon Tae-Hyuk, Lim Mi Hee
Department of Chemistry , Korea Advanced Institute of Science and Technology (KAIST) , Daejeon 34141 , Republic of Korea . Email:
Department of Chemistry , Ulsan National Institute of Science and Technology (UNIST) , Ulsan 44919 , Republic of Korea . Email:
Chem Sci. 2019 Jun 5;10(28):6855-6862. doi: 10.1039/c9sc00931k. eCollection 2019 Jul 28.
Amyloidogenic peptides are considered central pathological contributors towards neurodegeneration as observed in neurodegenerative disorders [, amyloid-β (Aβ) peptides in Alzheimer's disease (AD)]; however, their roles in the pathologies of such diseases have not been fully elucidated since they are challenging targets to be studied due to their heterogeneous nature and intrinsically disordered structure. Chemical approaches to modify amyloidogenic peptides would be valuable in advancing our molecular-level understanding of their involvement in neurodegeneration. Herein, we report effective chemical strategies for modification of Aβ peptides (, coordination and coordination-/photo-mediated oxidation) implemented by a single Ir(iii) complex in a photo-dependent manner. Such peptide variations can be achieved by our rationally designed Ir(iii) complexes (, , , and ) leading to significantly modulating the aggregation pathways of two main Aβ isoforms, Aβ and Aβ, as well as the production of toxic Aβ species. Overall, we demonstrate chemical tactics for modification of amyloidogenic peptides in an effective and manageable manner utilizing the coordination capacities and photophysical properties of transition metal complexes.
淀粉样生成肽被认为是神经退行性疾病中神经退行性变的核心病理因素（如阿尔茨海默病（AD）中的淀粉样β（Aβ）肽）；然而，由于其异质性本质和内在无序结构，它们在这类疾病病理中的作用尚未完全阐明，这使得它们成为具有挑战性的研究靶点。化学方法修饰淀粉样生成肽对于推进我们在分子水平上对其参与神经退行性变的理解将是有价值的。在此，我们报告了一种由单一铱（III）配合物以光依赖方式实施的有效化学策略，用于修饰Aβ肽（即配位以及配位/光介导氧化）。通过我们合理设计的铱（III）配合物（如 、 、 和 ）可以实现此类肽变体，从而显著调节两种主要Aβ异构体Aβ 和 Aβ 的聚集途径以及有毒Aβ物种的产生。总体而言，我们展示了利用过渡金属配合物的配位能力和光物理性质以有效且可控的方式修饰淀粉样生成肽的化学策略。
