Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogeno...Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters. Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes. After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples. This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish. Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources. In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research.展开更多
Iodinated boron dipyrromethene(BODIPY) dyes with 8-hydroxyl-quinoline or phenylamine moiety at the meso-position on the BODIPY core were used as efficient photosensitizers(PSs) of three-component light-driven producti...Iodinated boron dipyrromethene(BODIPY) dyes with 8-hydroxyl-quinoline or phenylamine moiety at the meso-position on the BODIPY core were used as efficient photosensitizers(PSs) of three-component light-driven production of H_2 system from acidic aqueous solution in conjunction with a cobaloxime[CoⅢ(dmgH)_2 PyCl](dmgH = dimethylglyoximate, and py = pyridine) as proton-reducing catalyst and ascorbic acid(H_2 A) as sacrificial electron donor. This is the first example of BODIPYs as homogeneous hydrogen-generating PSs employed in the acidic aqueous conditions. That they are active in the acidic solutions and inactive in the basic conditions may indicate that the extent of competition between intramolecular and intermolecular electron transfer reactions exists. Efficient bimolecular electron transfer reaction between PS and molecular catalyst is needed to make H_2 production, while the intramolecular electron transfer of PS may curb H_2 production. The results underscore that the chemical modification of BODIPYs can be performed, thus allowing for the transformation of acid and base conditions for the light-driven H_2 production.展开更多
基金supported by the National Natural Science Foundation of China(Nos. 21572029, 31600641,81703604, 81773687, 81672961 and 81573501)the National Key Research and Development Program of China (Nos. 2017YFC1700200 and 2017YFC1702000)+2 种基金Program of Shanghai Academic/Technology Research Leader(No. 18XD1403600)Shuguang Program (No. 18SG40)supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission and the Innovative Entrepreneurship Program of High-level Talents in Dalian (Nos. 2016RQ025 and 2017RQ121)
文摘Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters. Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes. After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples. This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish. Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources. In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research.
基金the National Natural Science Foundation of China (Nos. 21641011, 21571115 and 21701133)the Program for New Century Excellent Talents in Fujian Province University and the Fujian Key Laboratory of Functional Materials and Applications (No. fma2017107)+2 种基金the Natural Science Foundation of Shandong Province (No. JQ201803)Young Scholars Program of Shandong University (No. 2015WLJH24)the Fundamental Research Funds of Shandong University (No. 104.205.2.5) for financial support of this work
文摘Iodinated boron dipyrromethene(BODIPY) dyes with 8-hydroxyl-quinoline or phenylamine moiety at the meso-position on the BODIPY core were used as efficient photosensitizers(PSs) of three-component light-driven production of H_2 system from acidic aqueous solution in conjunction with a cobaloxime[CoⅢ(dmgH)_2 PyCl](dmgH = dimethylglyoximate, and py = pyridine) as proton-reducing catalyst and ascorbic acid(H_2 A) as sacrificial electron donor. This is the first example of BODIPYs as homogeneous hydrogen-generating PSs employed in the acidic aqueous conditions. That they are active in the acidic solutions and inactive in the basic conditions may indicate that the extent of competition between intramolecular and intermolecular electron transfer reactions exists. Efficient bimolecular electron transfer reaction between PS and molecular catalyst is needed to make H_2 production, while the intramolecular electron transfer of PS may curb H_2 production. The results underscore that the chemical modification of BODIPYs can be performed, thus allowing for the transformation of acid and base conditions for the light-driven H_2 production.
