An Activity-Based Near-Infrared Glucuronide Trapping Probe for Imaging beta-Glucuronidase Expression in Deep Tissues

doi:10.1021/ja209335z

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 藥學系(所) > 期刊論文 > Item 310902800/27685

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標題:	An Activity-Based Near-Infrared Glucuronide Trapping Probe for Imaging beta-Glucuronidase Expression in Deep Tissues
作者:	Cheng, Ta-Chun Roffler, Steve R. Tzou, Shey-Cherng Chuang, Kuo-Hsiang Su, Yu-Cheng Chuang, Chih-Hung Kao, Chien-Han Chen, Chien-Shu Harn, I-Hong Liu, Kuan-Yi Cheng, Tian-Lu Leu, Yu-Ling
貢獻者:	藥學系
關鍵字:	In-Vivo Reporter Gene Prodrug Monotherapy Antitumor-Activity Escherichia-Coli Cancer Optimization Activation Proteases Catalysis
日期:	2012-02-15
上傳時間:	2014-03-21 16:17:37 (UTC+8)
出版者:	Amer Chemical Soc
摘要:	beta-glucuronidase is an attractive reporter and prodrug-converting enzyme. The development of near-IR (NIR) probes for imaging of beta-glucuronidase activity would be ideal to allow estimation of reporter expression and for personalized glucuronide prodrug cancer therapy in preclinical studies. However, NIR glucuronide probes are not yet available. In this work, we developed two fluorescent probes for detection of beta-glucuronidase activity, one for the NIR range (containing IR-820 dye) and the other for the visible range [containing fluorescein isothiocyanate (FITC)], by utilizing a difluoromethylphenol-glucuronide moiety (TrapG) to trap the fluorochromes in the vicinity of the active enzyme. beta-glucuronidase-mediated hydrolysis of the glucuronyl bond of TrapG generates a highly reactive alkylating group that facilitates the attachment of the fluorochrome to nucleophilic moieties located near beta-glucuronidase-expressing sites. FITC-TrapG was selectively trapped on purified beta-glucuronidase or beta-glucuronidase-expressing CT26 cells (CT26/m beta G) but not on bovine serum albumin or non-beta-glucuronidase-expressing CT26 cells used as controls. beta-glucuronidase-activated FITC-TrapG did not interfere with beta-glucuronidase activity and could label bystander proteins near beta-glucuronidase. Both FITC-TrapG and NIR-TrapG specifically imaged subcutaneous CT26/m beta G tumors, but only NIR-TrapG could image CT26/m beta G tumors transplanted deep in the liver. Thus NIR-TrapG may provide a valuable tool for visualizing beta-glucuronidase activity in vivo.
關聯:	Journal of The American Chemical Society, 134(6), 3103-3110
顯示於類別:	[藥學系(所)] 期刊論文

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