Amyloid diseases are characterized by the aggregation of various proteins to form insoluble β-sheet-rich fibrils leading to cell death. Vibrational spectroscopies have emerged as attractive methods to study this process because of the rich structural information that can be extracted without large, perturbative probes. Importantly, specific vibrations such as the amide-I band directly report on secondary structure changes, which are key features of amyloid formation. Beyond intrinsic vibrations, the incorporation of unnatural vibrational probes can improve sensitivity for secondary structure determination (e.g. isotopic labeling), can provide residue-specific information of the surrounding polarity (e.g. unnatural amino acid), and are translatable into cellular studies. Here, we review the latest studies that have leveraged tools from chemical biology for the incorporation of novel vibrational probes into amyloidogenic proteins for both mechanistic and cellular studies.

中文翻译：

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耦合化学生物学和振动光谱，用于体外和细胞内淀粉样蛋白的研究。

淀粉样蛋白疾病的特征是各种蛋白质聚集形成不溶性富含β-折叠的原纤维，导致细胞死亡。振动光谱已成为研究这一过程的有吸引力的方法，因为无需大型微扰探针即可提取丰富的结构信息。重要的是，特定的振动，如酰胺-I 带直接报告二级结构变化，这是淀粉样蛋白形成的关键特征。除了固有振动之外，非天然振动探针的加入可以提高二级结构测定的灵敏度（例如同位素标记），可以提供周围极性的残基特异性信息（例如非天然氨基酸），并可转化为细胞研究。这里，