Rationally engineered IR-783 octanoate as an enzyme-activatable fluorogenic tool for functional imaging of h Notum in living systems  

作　　者：Lilin Song Mengru Sun Yuqing Song Feng Zhang Bei Zhao Hairong Zeng Jinhui Shi Huixin Liu Shanshan Zhao Tian Tian Heng Yin Guangbo Ge 

机构地区：[1]Liaoning Provincial Key Laboratory of Carbohydrates,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian 116023,China [2]Shanghai Frontiers Science Center of TCM Chemical Biology,Institute of Interdisciplinary Integrative Medicine Re-search,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [3]University of Chinese Academy of Sciences,Beijing 100049,China [4]Health Sciences Institute,China Medical University,Shenyang 110122,China [5]Department of Gynecology,Cancer Hospital of China Medical University,Liaoning Cancer Hospital&Institute,Shenyang 110042,China

出　　处：《Chinese Chemical Letters》2024年第11期442-447,共6页中国化学快报（英文版）

基　　金：supported by National Natural Science Foundation of China(Nos.81922070,81973286,82273897,U23A20516,81801818);Shanghai Municipal Health Commission’s TCM research project(No.2022CX005);Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTDD-202004);Three-year Action Plan for Shanghai TCM Development and Inheritance Program(No.ZY(2021-2023)-0401);Department of Science&Technology of Liaoning Province Grant(No.2022JH2/20200056);supported by the State Key Laboratory of Fine Chemicals;Dalian University of Technology(No.KF 2202)。

摘　　要：As a vital negative regulator of Wnt signaling pathway,human Notum(hNotum)plays a crucial regulatory role in the progression of many human diseases.Deciphering the relevance of h Notum to human diseases requires practical and reliable tools for visualizing h Notum activity in living systems.Herein,an enzyme-activatable fluorogenic tool(IR-783 octanoate)was rationally engineered for sensing and imaging h Notum activity in living systems by integrating computer-aided molecular design and biochemical assays.IR-783 octanoate showed good optical properties,excellent specificity and high binding-affinity towards h Notum(K_(m)=0.98μmol/L).IR-783 octanoate could be well up-taken into the cancerous cells or tumors that over-expressed organic anion transporting polypeptides(OATPs),and then hydrolyzed by cellular h Notum to release free IR-783 ketone,which created brightly fluorescent signals around 646 nm.Further investigations showed that IR-783 octanoate achieved a good performance for in-situ functional imaging of h Notum in both living cells,cancerous tissues and organs.It was also found that some SW620cells with multipolar spindles could be stained by IR-783 octanoate to emit extremely bright signals,suggesting that this agent could be used as a novel visualizing tool for tracing the cells undergoing abnormal cell mitoses.Collectively,this study devises a highly specific fluorogenic tool for in-situ functional imaging of hNotum in living systems,which offers a practical and reliable tool to dynamically track the changes in h Notum activity under various conditions.

关 键 词：hNotum Optical substrate Computer-aided molecular design In-situ functional imaging Cancer diagnosis 

分 类 号：O657.3[理学—分析化学] Q503[理学—化学]