Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.
Chembiochem. 2023 Jun 1;24(11):e202300044. doi: 10.1002/cbic.202300044. Epub 2023 May 8.
The development of ligands for detecting protein aggregates is of great interest, as these aggregated proteinaceous species are the pathological hallmarks of several devastating diseases, including Alzheimer's disease. In this regard, thiophene-based ligands have emerged as powerful tools for fluorescent assessment of these pathological entities. The intrinsic conformationally sensitive photophysical properties of poly- and oligothiophenes have allowed optical assignment of disease-associated protein aggregates in tissue sections, as well as real-time in vivo imaging of protein deposits. Herein, we recount the chemical evolution of different generations of thiophene-based ligands, and exemplify their use for the optical distinction of polymorphic protein aggregates. Furthermore, the chemical determinants for achieving a superior fluorescent thiophene-based ligand, as well as the next generation of thiophene-based ligands targeting distinct aggregated species are described. Finally, the directions for future research into the chemical design of thiophene-based ligands that can aid in resolving the scientific challenges around protein aggregation diseases are discussed.
开发用于检测蛋白质聚集体的配体具有重要意义，因为这些聚集的蛋白质物种是包括阿尔茨海默病在内的几种破坏性疾病的病理标志。在这方面，噻吩基配体已成为荧光评估这些病理实体的有力工具。聚噻吩和寡噻吩的固有构象敏感光物理性质允许在组织切片中对与疾病相关的蛋白质聚集体进行光学分配，以及实时在体内对蛋白质沉积物进行成像。在此，我们叙述了不同代噻吩基配体的化学演变，并举例说明了它们在光学区分多晶型蛋白质聚集体方面的应用。此外，还描述了实现优越荧光噻吩基配体的化学决定因素，以及针对不同聚集物种的下一代噻吩基配体。最后，讨论了未来在噻吩基配体的化学设计方面的研究方向，这有助于解决蛋白质聚集疾病周围的科学挑战。
