Department of Chemistry, Koç University, 34450 Istanbul, Turkey.
Department of Chemistry, Beckman Institute for Advanced Science and Technology, and Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
J Mater Chem B. 2024 Jan 31;12(5):1149-1167. doi: 10.1039/d3tb02468g.
Butyrylcholinesterase (BChE), a member of the human serine hydrolase family, is an essential enzyme for cholinergic neurotransmission as it catalyzes the hydrolysis of acetylcholine. It also plays central roles in apoptosis, lipid metabolism, and xenobiotic detoxification. On the other side, abnormal levels of BChE are directly associated with the formation of pathogenic states such as neurodegenerative diseases, psychiatric and cardiovascular disorders, liver damage, diabetes, and cancer. Thus, selective and sensitive detection of BChE level in living organisms is highly crucial and is of great importance to further understand the roles of BChE in both physiological and pathological processes. However, it is a very complicated task due to the potential interference of acetylcholinesterase (AChE), the other human cholinesterase, as these two enzymes share a very similar substrate scope. To this end, optical imaging probes have attracted immense attention in recent years as they have modular structures, which can be tuned precisely to satisfy high selectivity toward BChE, and at the same time they offer real time and nondestructive imaging opportunities with a high spatial and temporal resolution. Here, we summarize BChE selective imaging probes by discussing the critical milestones achieved during the development process of these molecular sensors over the years. We put a special emphasis on design principles and biological applications of highly promising new generation activity-based probes. We also give a comprehensive outlook for the future of BChE-responsive probes and highlight the ongoing challenges. This collection marks the first review article on BChE-responsive imaging agents.
丁酰胆碱酯酶（BChE）是人类丝氨酸水解酶家族的一员，作为一种关键酶，它可催化乙酰胆碱的水解，从而在胆碱能神经传递中发挥作用。它还在细胞凋亡、脂质代谢和外来生物解毒中发挥核心作用。另一方面，BChE 水平的异常与神经退行性疾病、精神和心血管疾病、肝损伤、糖尿病和癌症等致病状态的形成直接相关。因此，在生物体中选择性和灵敏地检测 BChE 水平非常重要，这对于进一步了解 BChE 在生理和病理过程中的作用具有重要意义。然而，由于另一种人类胆碱酯酶——乙酰胆碱酯酶（AChE）的潜在干扰，这是一项非常复杂的任务，因为这两种酶具有非常相似的底物范围。为此，光学成像探针近年来受到了极大的关注，因为它们具有模块化结构，可以精确调整以满足对 BChE 的高选择性，同时提供具有高时空分辨率的实时和无损成像机会。在这里，我们通过讨论这些分子传感器在多年的发展过程中所取得的关键里程碑，总结了 BChE 选择性成像探针。我们特别强调了新一代基于活性的探针的设计原理和生物应用。我们还对 BChE 响应性探针的未来进行了全面展望，并强调了当前的挑战。这一系列标志着第一篇关于 BChE 响应性成像剂的综述文章。
