Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Chem Commun (Camb). 2020 Mar 24;56(24):3567-3570. doi: 10.1039/c9cc09849f.
Fluorescent small molecules are powerful tools for imaging α-synuclein pathology in vitro and in vivo. In this work, we explore benzofuranone as a potential scaffold for the design of fluorescent α-synuclein probes. These compounds have high affinity for α-synuclein, show fluorescent turn-on upon binding to fibrils, and display different binding to Lewy bodies, Lewy neurites and glial cytoplasmic inclusion pathologies in post-mortem brain tissue. These studies not only reveal the potential of benzofuranone compounds as α-synuclein specific fluorescent probes, but also have implications for the ways in which α-synucleinopathies are conformationally different and display distinct small molecule binding sites.
荧光小分子是体外和体内成像α-突触核蛋白病理的有力工具。在这项工作中，我们探索苯并呋喃酮作为设计荧光α-突触核蛋白探针的潜在支架。这些化合物对α-突触核蛋白具有高亲和力，与纤维结合时表现出荧光开启，并在死后脑组织中显示出不同的与路易体、路易神经突和神经胶质细胞质包涵体病理学的结合。这些研究不仅揭示了苯并呋喃酮化合物作为α-突触核蛋白特异性荧光探针的潜力，而且对α-突触核蛋白病的构象差异和显示不同的小分子结合位点的方式具有启示意义。
