Hydrogen peroxide(H2O2)plays a significant role in regulating a variety of biological processes.Dysregulation of H2O2 can lead to various diseases.Although numerous fluorescent imaging probes for H2O2 have been report...Hydrogen peroxide(H2O2)plays a significant role in regulating a variety of biological processes.Dysregulation of H2O2 can lead to various diseases.Although numerous fluorescent imaging probes for H2O2 have been reported,the development of H2O2 ratiometric fluorescent probe with large Stokes shift remains rather limited.Such probes have shown distinct advantages,such as minimized interference from environment and improved signal-to noise ratio.In this work,we reported a new pyrene-based compound Py-VPB as H2O2 fluorescent probe in vitro.The probe demonstrated ratiometric detection behavior,large Stokes shift and large emission shift.In addition,the probe showed high sensitivity and selectivity towards H2O2 in vitro.Based on these excellent properties,we successfully applied Py-VPB to the visualization of exogenous and endogenous H2O2 in living cells.Cell imaging study also showed that our probe was localized in the mitochondria.We envision that the probe can provide a useful tool for unmasking the biological roles of mitochondrial H2O2 in living systems.展开更多
Many cyclobutane natural products have intriguing biological properties that arise from their fascinating chemical structures.Cyclobutane natural products feature a cyclobutane scaffold as the core or as a part of the...Many cyclobutane natural products have intriguing biological properties that arise from their fascinating chemical structures.Cyclobutane natural products feature a cyclobutane scaffold as the core or as a part of the spirocyclic or fused cyclic core.However,the highly functionalized nature and the inherent stereochemistry of these cyclobutane natural products,which are associated with their biological activities,pose tremendous challenges to their preparation.In this perspective,we present contemporary advancements in synthetic methods and/or strategies en route to the bioactive cyclobutane natural products.We begin by describing the representative bioactive cyclobutane natural products and then focus on illustrative examples of their syntheses reported from 2018 to 2021.These advances will enable efficient syntheses of cyclobutanes of structural and biological importance.展开更多
Lysine lipoylation plays vital roles in cell metabolism and redox processes.For example,removal of lipoylation will decrease pyruvate dehydrogenase activity and affect the citric acid cycle.Despite the important funct...Lysine lipoylation plays vital roles in cell metabolism and redox processes.For example,removal of lipoylation will decrease pyruvate dehydrogenase activity and affect the citric acid cycle.Despite the important functions of lysine lipoylation,the mechanisms for the addition and removal of this modification remain largely unexplored.Very few useful chemical tools are available to study the interactions of lysine lipoylation with its regulatory delipoylation proteins.For example,immunoaffinity purification-mass spectrometry is one of such tools,which highly relies on antibody efficiency and purification techniques.Single-step activity based fluorogenic probes developed by our groups and others is also an efficient method to study the deacylation activity.Affinitybased labeling probe using photo-cross-linker is a powerful platform to study the transient and dynamic interactions of peptide ligands with the interacting proteins.Herein,we have designed and synthesized a dual-function probe KTLlip for studying enzymatic delipoylation(eraser)activity and interaction of lysine lipoylation with the eraser at the same time.We show that KTLlip can be used as a useful tool to detect delipoylation as demonstrated by its ability to fluorescently label the eraser activity of recombinant Sirt2.We envision that the probe will help delineate the roles of delipoylation enzyme in biology.展开更多
Microarray technology has been widely applied in biomedical research.The key to microarray study is to develop efficient immobilization method.In this study,we designed a new reversible microarray immobilization metho...Microarray technology has been widely applied in biomedical research.The key to microarray study is to develop efficient immobilization method.In this study,we designed a new reversible microarray immobilization method based on thiol-quinone reaction.A quinone-functionalized slide was fabricated through H_(2)O_(2)treatment of dopamine-coated slides.Various thiol-containing molecules can be anchored onto the quinone-functionalized slides via thioether linker,which could be cleaved under H_(2)O_(2) treatment to regenerate quinone groups on the surface.The highly versatile approach can be widely used for immobilization of various thiol-containing molecules.展开更多
基金This work was supported by the Science Technology and Innovation Committee of Shenzhen Municipality(JCYJ20180507181654823)the National Natural Science Foundation of China(21778044)and Sichuan Science and Technology Program(2018JY0360).
文摘Hydrogen peroxide(H2O2)plays a significant role in regulating a variety of biological processes.Dysregulation of H2O2 can lead to various diseases.Although numerous fluorescent imaging probes for H2O2 have been reported,the development of H2O2 ratiometric fluorescent probe with large Stokes shift remains rather limited.Such probes have shown distinct advantages,such as minimized interference from environment and improved signal-to noise ratio.In this work,we reported a new pyrene-based compound Py-VPB as H2O2 fluorescent probe in vitro.The probe demonstrated ratiometric detection behavior,large Stokes shift and large emission shift.In addition,the probe showed high sensitivity and selectivity towards H2O2 in vitro.Based on these excellent properties,we successfully applied Py-VPB to the visualization of exogenous and endogenous H2O2 in living cells.Cell imaging study also showed that our probe was localized in the mitochondria.We envision that the probe can provide a useful tool for unmasking the biological roles of mitochondrial H2O2 in living systems.
基金J.Liu acknowledges the support of the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515010188)the Shenzhen Science and Technology Innovation Committee(No.JCYJ20190809181011411)+1 种基金the Guangdong Department of Education(No.2021ZDJS097)Y.Xie gratefully acknowledges the financial support from the National Natural Science Foundation of China(No.22107058).
文摘Many cyclobutane natural products have intriguing biological properties that arise from their fascinating chemical structures.Cyclobutane natural products feature a cyclobutane scaffold as the core or as a part of the spirocyclic or fused cyclic core.However,the highly functionalized nature and the inherent stereochemistry of these cyclobutane natural products,which are associated with their biological activities,pose tremendous challenges to their preparation.In this perspective,we present contemporary advancements in synthetic methods and/or strategies en route to the bioactive cyclobutane natural products.We begin by describing the representative bioactive cyclobutane natural products and then focus on illustrative examples of their syntheses reported from 2018 to 2021.These advances will enable efficient syntheses of cyclobutanes of structural and biological importance.
基金supported by the Science Technology and Innovation Committee of Shenzhen Municipality(Grant Nos.JCYJ20180507181654823 and JCYJ20170413141047772)the National Natural Science Foundation of China(Grant No.21778044).
文摘Lysine lipoylation plays vital roles in cell metabolism and redox processes.For example,removal of lipoylation will decrease pyruvate dehydrogenase activity and affect the citric acid cycle.Despite the important functions of lysine lipoylation,the mechanisms for the addition and removal of this modification remain largely unexplored.Very few useful chemical tools are available to study the interactions of lysine lipoylation with its regulatory delipoylation proteins.For example,immunoaffinity purification-mass spectrometry is one of such tools,which highly relies on antibody efficiency and purification techniques.Single-step activity based fluorogenic probes developed by our groups and others is also an efficient method to study the deacylation activity.Affinitybased labeling probe using photo-cross-linker is a powerful platform to study the transient and dynamic interactions of peptide ligands with the interacting proteins.Herein,we have designed and synthesized a dual-function probe KTLlip for studying enzymatic delipoylation(eraser)activity and interaction of lysine lipoylation with the eraser at the same time.We show that KTLlip can be used as a useful tool to detect delipoylation as demonstrated by its ability to fluorescently label the eraser activity of recombinant Sirt2.We envision that the probe will help delineate the roles of delipoylation enzyme in biology.
基金the financial support from the Research Grants Council of Hong Kong(Nos.11102719,11304118 and 14306317)Shenzhen Basic Research Project(No.JCYJ20160601173218804)+1 种基金National Natural Science Foundation of China(No.21778044)the Shandong University of Technology Ph.D.Startup Foundation(No.420033)。
文摘Microarray technology has been widely applied in biomedical research.The key to microarray study is to develop efficient immobilization method.In this study,we designed a new reversible microarray immobilization method based on thiol-quinone reaction.A quinone-functionalized slide was fabricated through H_(2)O_(2)treatment of dopamine-coated slides.Various thiol-containing molecules can be anchored onto the quinone-functionalized slides via thioether linker,which could be cleaved under H_(2)O_(2) treatment to regenerate quinone groups on the surface.The highly versatile approach can be widely used for immobilization of various thiol-containing molecules.