hoton emission properties of polyphenylphenol (PPP) synthesized in the pres-ence of a newly-found enzymatic catalyst are reported. The photoluminescence peakexcited by the light at 350 nm is at about 370-420 nm. The a...hoton emission properties of polyphenylphenol (PPP) synthesized in the pres-ence of a newly-found enzymatic catalyst are reported. The photoluminescence peakexcited by the light at 350 nm is at about 370-420 nm. The absorption band edgesand photon emitting peaks of the polymer were found dependent on the conjugatedlengths of the polymer. In the transient luminescence measurement the lifetime ofPL decay was determined to be 2. 0 ns which is supposed as the evidence of polaronexcitation recombination.展开更多
An electrochemical immunosensor was developed for sensitive assay ofE. coli in urban sludge, in which electron mediator-mediated enzymatic catalysis and gold nanoparticles(AuNPs) were utilized for signal amplificati...An electrochemical immunosensor was developed for sensitive assay ofE. coli in urban sludge, in which electron mediator-mediated enzymatic catalysis and gold nanoparticles(AuNPs) were utilized for signal amplification. The immnuosensing platform chitosan-thionine(chit-thio)/poly(amidoamine) dendrimer-encapsulated AuNPs [PAMAM(Au)] composites were first prepared from chit-thio and PAMAM(Au) using the layer-by-layer method to provide a matrix for high-stability and high-bioactivity bindings of the capture antibody(cAb). Moreover, the {dAb-AuNPs-HRP} nanoprobes were designed to exploit the amplification effect of the carrier AuNPs due to the loading amounts of horseradish peroxidase(HRP)and the detection antibody(dAb). The sandwich-type immunoassay was then successfully used to assay E. coli based on the oxidation of thionine as a result of H2O2-induced enzymatic catalytic reaction by HRP. This study presents a powerful tool in electrochemical immunoassay for E. coli detection with rapid response, high-sensitivity and high-specificity, providing a potential new tool for feasibility assessment of sludge recycle.展开更多
Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides supply.However,the catalytic potential and structural basis of plant malonyltransferase are far...Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides supply.However,the catalytic potential and structural basis of plant malonyltransferase are far from being fully elucidated.This work identified a new malonyltransferase CtMaT1 from Cistanche tubulosa.It displayed unprecedented mono-and/or di-malonylation activity toward diverse glucosides with different aglycons.A“one-pot”system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated glucosides.Structural investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse glucosides.Additionally,it recognizes malonyl-CoA through strong electrotactic and hydrogen interactions.QM/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1,while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167,resulting in its high malonylation regiospecificity.Calculated energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for glucosides.Furthermore,a mutant CtMaT1H36A with notably increased di-malonylation activity was obtained.The underlying molecular mechanism was illuminated through MM/GBSA binding free energy calculation.This study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives,while also providing a versatile tool for enzymatic malonylation applications in pharmacology.展开更多
Chiral benzothiazepines constitute the core structures of many foremost pharmaceuticals with diverse biological activities endowed by their unique scaffolds,which poses a great challenge to organic chemists and pharma...Chiral benzothiazepines constitute the core structures of many foremost pharmaceuticals with diverse biological activities endowed by their unique scaffolds,which poses a great challenge to organic chemists and pharmaceutical researchers.This review provides a concise overview for the asymmetric synthesis of chiral benzothiazepine derivatives,focusing on advances in asymmetric catalysis,including metal catalysis,small-molecule organocatalysis and enzymatic catalysis.The catalytic asymmetric reactions,involving asymmetric epoxidation,reduction,dihydroxylation,hydrogenation,aldol reaction and other sulfa-Michael addition,have emerged as powerful strategies for the rapid construction of chiral benzothiazepine through single or multistep reactions.The booming asymmetric synthetic methodology affords us instructive clues for the highly efficient preparation of chiral benzothiazepines,facilitating their large-scale preparation and diversity-oriented synthesis.展开更多
Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delive...Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity.Moreover,for the intracellularly acted proteins,cell membrane as a primary barrier hinders the transmembrane delivery of proteins.The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes.We herein develop a proteasemanipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins.The embedded polymeric nanogels(CytoC/aNGs)preserve activity of cytochrome c(CytoC)that is an intracellular activator for cell apoptosis as a model protein against proteolysis,and do not affect the gelation properties of the protease-catalysis assembled hydrogels.The injectable hydrogel(CytoC/aNGs/Gel)serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs.The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site,cytoplasm,resulting in favorable apoptosis-inducing and cytotoxic effects.We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.展开更多
A simple and efficient method using enzyme immobilized microfluidic channel as open tubular microreactor was designed for amperometric detection of glucose. The microreactor was composed of a polydimethylsilicone/ gla...A simple and efficient method using enzyme immobilized microfluidic channel as open tubular microreactor was designed for amperometric detection of glucose. The microreactor was composed of a polydimethylsilicone/ glass hybrid device with three reservoirs, a cooling cave and a 6 cm capillary with a sampling fracture as micro-channel. The microchannel was further modified by thermal polymerization, followed by covalently attaching with glucose oxidase. Through fracture sampling and electrochromatography separation, the production via enzymatic reaction was determinated by Pt electrode at the end of capillary. The linear range for the detection of glucose was 0.05--7.5 mmol·L-1 with detection limit of 23μmol.L-1 The inter-and intra-chip reproducibilities for determination of 2.5 mmol-L-1 glucose were 98.5% (n=5) and 96.0% (n=5), respectively. With the advantage of flexible assembly, rapid efficiency, good stability and low-cost, this microreactor provided a potential platform for estab- lishing a portable enzyme-based chemical detection system in practical application.展开更多
文摘hoton emission properties of polyphenylphenol (PPP) synthesized in the pres-ence of a newly-found enzymatic catalyst are reported. The photoluminescence peakexcited by the light at 350 nm is at about 370-420 nm. The absorption band edgesand photon emitting peaks of the polymer were found dependent on the conjugatedlengths of the polymer. In the transient luminescence measurement the lifetime ofPL decay was determined to be 2. 0 ns which is supposed as the evidence of polaronexcitation recombination.
基金Supported by the National Natural Science Foundation of China(Nos.21205051, 51608235) and the Key Project of the Ministry of Education of China(No.210078).
文摘An electrochemical immunosensor was developed for sensitive assay ofE. coli in urban sludge, in which electron mediator-mediated enzymatic catalysis and gold nanoparticles(AuNPs) were utilized for signal amplification. The immnuosensing platform chitosan-thionine(chit-thio)/poly(amidoamine) dendrimer-encapsulated AuNPs [PAMAM(Au)] composites were first prepared from chit-thio and PAMAM(Au) using the layer-by-layer method to provide a matrix for high-stability and high-bioactivity bindings of the capture antibody(cAb). Moreover, the {dAb-AuNPs-HRP} nanoprobes were designed to exploit the amplification effect of the carrier AuNPs due to the loading amounts of horseradish peroxidase(HRP)and the detection antibody(dAb). The sandwich-type immunoassay was then successfully used to assay E. coli based on the oxidation of thionine as a result of H2O2-induced enzymatic catalytic reaction by HRP. This study presents a powerful tool in electrochemical immunoassay for E. coli detection with rapid response, high-sensitivity and high-specificity, providing a potential new tool for feasibility assessment of sludge recycle.
基金This work was financially supported by National Key Research and Development Program Special Project of Synthetic Biology(Grant No.2023YFA0914100/2023YFA0914103)National Natural Science Foundation of China(Grant No.82173922,81402809)+3 种基金Beijing Natural Science Foundation(Grant No.7192112)Fundamental Research Funds for the Central Universities(Grant No.2023-JYB-JBQN-054,China)Young Elite Scientists Sponsorship Program by CAST(Grant No.CACM-2018-QNRC1-02,China)State Key Laboratory of Natural and Biomimetic Drugs Foundation(Grant No.K202119,China).
文摘Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides supply.However,the catalytic potential and structural basis of plant malonyltransferase are far from being fully elucidated.This work identified a new malonyltransferase CtMaT1 from Cistanche tubulosa.It displayed unprecedented mono-and/or di-malonylation activity toward diverse glucosides with different aglycons.A“one-pot”system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated glucosides.Structural investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse glucosides.Additionally,it recognizes malonyl-CoA through strong electrotactic and hydrogen interactions.QM/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1,while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167,resulting in its high malonylation regiospecificity.Calculated energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for glucosides.Furthermore,a mutant CtMaT1H36A with notably increased di-malonylation activity was obtained.The underlying molecular mechanism was illuminated through MM/GBSA binding free energy calculation.This study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives,while also providing a versatile tool for enzymatic malonylation applications in pharmacology.
基金The support from the National Natural Science Foundation of China(No.21877087)is greatly appreciated.
文摘Chiral benzothiazepines constitute the core structures of many foremost pharmaceuticals with diverse biological activities endowed by their unique scaffolds,which poses a great challenge to organic chemists and pharmaceutical researchers.This review provides a concise overview for the asymmetric synthesis of chiral benzothiazepine derivatives,focusing on advances in asymmetric catalysis,including metal catalysis,small-molecule organocatalysis and enzymatic catalysis.The catalytic asymmetric reactions,involving asymmetric epoxidation,reduction,dihydroxylation,hydrogenation,aldol reaction and other sulfa-Michael addition,have emerged as powerful strategies for the rapid construction of chiral benzothiazepine through single or multistep reactions.The booming asymmetric synthetic methodology affords us instructive clues for the highly efficient preparation of chiral benzothiazepines,facilitating their large-scale preparation and diversity-oriented synthesis.
基金supported by the National Key Research and Development Program of China(No.2019YFA0905200)the National Natural Science Foundation of China(No.81971730,No.81503012)+1 种基金the Natural Science Foundation of Jiangsu Province of China for Excellent Young Scholars(No.BK20190084)the Young Elite Scientists Sponsorship Program by CAST(China)
文摘Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity.Moreover,for the intracellularly acted proteins,cell membrane as a primary barrier hinders the transmembrane delivery of proteins.The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes.We herein develop a proteasemanipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins.The embedded polymeric nanogels(CytoC/aNGs)preserve activity of cytochrome c(CytoC)that is an intracellular activator for cell apoptosis as a model protein against proteolysis,and do not affect the gelation properties of the protease-catalysis assembled hydrogels.The injectable hydrogel(CytoC/aNGs/Gel)serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs.The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site,cytoplasm,resulting in favorable apoptosis-inducing and cytotoxic effects.We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.
文摘A simple and efficient method using enzyme immobilized microfluidic channel as open tubular microreactor was designed for amperometric detection of glucose. The microreactor was composed of a polydimethylsilicone/ glass hybrid device with three reservoirs, a cooling cave and a 6 cm capillary with a sampling fracture as micro-channel. The microchannel was further modified by thermal polymerization, followed by covalently attaching with glucose oxidase. Through fracture sampling and electrochromatography separation, the production via enzymatic reaction was determinated by Pt electrode at the end of capillary. The linear range for the detection of glucose was 0.05--7.5 mmol·L-1 with detection limit of 23μmol.L-1 The inter-and intra-chip reproducibilities for determination of 2.5 mmol-L-1 glucose were 98.5% (n=5) and 96.0% (n=5), respectively. With the advantage of flexible assembly, rapid efficiency, good stability and low-cost, this microreactor provided a potential platform for estab- lishing a portable enzyme-based chemical detection system in practical application.