Mercury ion(Hg^(2+)),a highly noxious of heavy metalion,has detrimental effects on the ecological environment and human health.Herein,we have developed an exonuclease III(Exo III)assisted catalytic hairpin assembly fo...Mercury ion(Hg^(2+)),a highly noxious of heavy metalion,has detrimental effects on the ecological environment and human health.Herein,we have developed an exonuclease III(Exo III)assisted catalytic hairpin assembly formation of a trivalent G-quadruplex/hemin DNAzyme for colorimetric detection of Hg^(2+).A hairpin DNA(Hr)was designed with thymine-Hg^(2+)-thymine pairs that catalyzed by Exo III is prompted to happen upon binding Hg^(2+).A released DNA fragment triggers the catalytic assembly of other three hairpins(H1,H2,and H3)to form many trivalent G-quadruplex/hemin DNA enzymes for signal output.The developed sensor shows a dynamic range from 2 pM to 2μM,with an impressively low detection limit of 0.32 pM for Hg^(2+)detection.Such a sensor also has good selectivity toward Hg^(2+)detection in the presence of other common metal ions.This strategy shows the great potential for visual detection with portable type.展开更多
DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especi...DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.展开更多
A heroin-binding DNA G-quadruplex （also known as a heroin aptamer or DNAzyme） has been previously re- ported to be able to enhance the peroxidase activity of heroin. In this work, we described a DNAzyme structure th...A heroin-binding DNA G-quadruplex （also known as a heroin aptamer or DNAzyme） has been previously re- ported to be able to enhance the peroxidase activity of heroin. In this work, we described a DNAzyme structure that had an effector-recognizing part appearing as a single stranded DNA linkage flanked by two split G-quadruplex halves. Hybridization of the single stranded part in the enzyme with a perfectly matched DNA strand （effector） formed a rigid DNA duplex between the two G-quadruplex halves and thus efficiently suppressed the enzymatic activity of the G-quadruplex/hemin complex, while the mismatched effector strand was not able to regulate the peroxidase activity effectively. With 2,2＇-azinobis（3-ethylbenzthiazoline）-6-sulfonic acid （ABTS） as an oxidizable substrate, we were able to characterize the formation of the re-engineered G-quadruplex/hemin complex and verify its switchable peroxidase activity. Our results show that the split G-quadruplex is an especially useful module to design low-cost and label-free sensors toward various biologically or environmentally interesting targets.展开更多
G-quadruplexes(GQs) are guanine-rich, non-canonical nucleic acid structures that play fundamental roles in biological processes. Their structure and function are strongly influenced by their hydration shells. Although...G-quadruplexes(GQs) are guanine-rich, non-canonical nucleic acid structures that play fundamental roles in biological processes. Their structure and function are strongly influenced by their hydration shells. Although extensively studied through various experimental and computational methods, hydration patterns near DNA remain under debate due to the chemically and topologically heterogeneous nature of the exposed surface. In this work, we employed all-atom molecular dynamics(MD) simulation to study the hydration patterns of GQ DNA. The Drude oscillator model was used in MD simulation as a computationally efficient method for modeling electronic polarization in DNA ion solutions. Hydration structure was analyzed in terms of radial distribution functions and high-density three-dimensional hydration sites. Analysis of hydration dynamics focused on self-diffusion rates and orientation time correlation at different structural regions of GQ DNA.The results show highly heterogeneous hydration patterns in both structure and dynamics;for example, there are several insular high-density sites in the inner channel, and ‘spine of water’ in the groove. For water inside the loop, anomalous diffusion is present over a long time scale, but for water around the phosphate group and groove, diffusion becomes normal after ~30 ps. These essentially correspond to deeply buried structural water and strong interaction with DNA, respectively.展开更多
Genomic instability and inflammation are considered to be two enabling characteristics that support cancer development and progression.G-quadruplex structure is a key element that contributes to genomic instability an...Genomic instability and inflammation are considered to be two enabling characteristics that support cancer development and progression.G-quadruplex structure is a key element that contributes to genomic instability and inflammation.G-quadruplexes were once regarded as simply an obstacle that can block the transcription of oncogenes.A ligand targeting G-quadruplexes was found to have anticancer activity,making G-quadruplexes potential anticancer targets.However,further investigation has revealed that G-quadruplexes are widely distributed throughout the human genome and have many functions,such as regulating DNA replication,DNA repair,transcription,translation,epigenetics,and inflammatory response.G-quadruplexes play double regulatory roles in transcription and translation.In this review,we focus on G-quadruplexes as novel targets for the treatment of gastrointestinal cancers.We summarize the application basis of G-quadruplexes in gastrointestinal cancers,including their distribution sites,structural characteristics,and physiological functions.We describe the current status of applications for the treatment of esophageal cancer,pancreatic cancer,hepatocellular carcinoma,gastric cancer,colorectal cancer,and gastrointestinal stromal tumors,as well as the associated challenges.Finally,we review the prospective clinical applications of G-quadruplex targets,providing references for targeted treatment strategies in gastrointestinal cancers.展开更多
使用含有偕胺肟基团的改性聚丙烯腈(PAN)纤维作为载体材料,通过轴向配位作用负载氯化血红素(hemin)制备了非均相催化剂hemin-PAN,重点对其在有机染料氧化降解反应中的催化性能进行研究。结果表明,hemin-PAN能够通过活化H2O2催化染料的...使用含有偕胺肟基团的改性聚丙烯腈(PAN)纤维作为载体材料,通过轴向配位作用负载氯化血红素(hemin)制备了非均相催化剂hemin-PAN,重点对其在有机染料氧化降解反应中的催化性能进行研究。结果表明,hemin-PAN能够通过活化H2O2催化染料的氧化降解反应,其催化活性与纤维中偕胺肟基团数量密切相关,PAN增重率为14.9%时,hemin-PAN有最高的催化活性;增加催化剂hemin负载量或提高反应温度都有利于染料的氧化降解反应,hemin-PAN(增重率为14.9%,hemin负载量为0.026 mmol/g)催化罗丹明B染料氧化降解反应的活化能为63.83 k J/mol。展开更多
The insufficient internal resorption of iodide ions(I−)leads to thyroid disorders,such as goiter,hypothyroidism,and cretinism in adults.In this paper,a portable point-of-care testing(POCT)platform was developed for th...The insufficient internal resorption of iodide ions(I−)leads to thyroid disorders,such as goiter,hypothyroidism,and cretinism in adults.In this paper,a portable point-of-care testing(POCT)platform was developed for the dual-modal analysis of I^(−),seamlessly integrating both colorimetric and photothermal thermometer techniques.The quantification of results was achieved using a standard thermometer or smartphone.G-Quadruplex/Hemin(G4/Hemin)is the DNAzyme with peroxidase-like activity.The catalytic efficacy of G-quadruplex structures can be enhanced with the help of I^(−),manifesting as multicolor transitions from colorless to green and then blue,and accompanied by the increase of temperature,which can be used for the quantitative detection of I^(−).Additionally,digital analysis according to the three-color channels(R/G/B)by a cellphone eliminated the requirement for intricate instruments.This dual-modal method for portable I^(−)determination is cost-effectiveness,simplicity,remarkable sensitivity(0.5 nmol/L)and selectivity.Besides,it was applied to determining the concentration of I^(−)in spiked serum samples.展开更多
基金Supported by The Science and Technology Project of General Administration of Quality Supervision,Inspection and Quarantine (2015IK126)The Science and Technology Project of Changsha City of Hunan Province of China (KQ1602124).
文摘Mercury ion(Hg^(2+)),a highly noxious of heavy metalion,has detrimental effects on the ecological environment and human health.Herein,we have developed an exonuclease III(Exo III)assisted catalytic hairpin assembly formation of a trivalent G-quadruplex/hemin DNAzyme for colorimetric detection of Hg^(2+).A hairpin DNA(Hr)was designed with thymine-Hg^(2+)-thymine pairs that catalyzed by Exo III is prompted to happen upon binding Hg^(2+).A released DNA fragment triggers the catalytic assembly of other three hairpins(H1,H2,and H3)to form many trivalent G-quadruplex/hemin DNA enzymes for signal output.The developed sensor shows a dynamic range from 2 pM to 2μM,with an impressively low detection limit of 0.32 pM for Hg^(2+)detection.Such a sensor also has good selectivity toward Hg^(2+)detection in the presence of other common metal ions.This strategy shows the great potential for visual detection with portable type.
基金supported by the National Institutes of Health(R01CA177585,U01CA240346,and R01CA153821)(DY)the Purdue Center for Cancer Research(P30CA023168)+2 种基金the National Natural Science Foundation of China(82173707 and 82322065)the Program for Jiangsu Province Innovative Research Scholar(JSSCRC2021512)the“Double First-Class”University Project(CPUQNJC22_08).
文摘DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.
基金Acknowledgement This work was supported by National Natural Science Foundation of China （N o. 20605019）, PCSIRT （No IRT0756） and the Natural Science Foundation of Anhui Province Ministry of Education （No. K J20 1 2B 169）.
文摘A heroin-binding DNA G-quadruplex （also known as a heroin aptamer or DNAzyme） has been previously re- ported to be able to enhance the peroxidase activity of heroin. In this work, we described a DNAzyme structure that had an effector-recognizing part appearing as a single stranded DNA linkage flanked by two split G-quadruplex halves. Hybridization of the single stranded part in the enzyme with a perfectly matched DNA strand （effector） formed a rigid DNA duplex between the two G-quadruplex halves and thus efficiently suppressed the enzymatic activity of the G-quadruplex/hemin complex, while the mismatched effector strand was not able to regulate the peroxidase activity effectively. With 2,2＇-azinobis（3-ethylbenzthiazoline）-6-sulfonic acid （ABTS） as an oxidizable substrate, we were able to characterize the formation of the re-engineered G-quadruplex/hemin complex and verify its switchable peroxidase activity. Our results show that the split G-quadruplex is an especially useful module to design low-cost and label-free sensors toward various biologically or environmentally interesting targets.
基金supported by the National Natural Science Foundation of China (Grant Nos. 11705160 and 11647074)。
文摘G-quadruplexes(GQs) are guanine-rich, non-canonical nucleic acid structures that play fundamental roles in biological processes. Their structure and function are strongly influenced by their hydration shells. Although extensively studied through various experimental and computational methods, hydration patterns near DNA remain under debate due to the chemically and topologically heterogeneous nature of the exposed surface. In this work, we employed all-atom molecular dynamics(MD) simulation to study the hydration patterns of GQ DNA. The Drude oscillator model was used in MD simulation as a computationally efficient method for modeling electronic polarization in DNA ion solutions. Hydration structure was analyzed in terms of radial distribution functions and high-density three-dimensional hydration sites. Analysis of hydration dynamics focused on self-diffusion rates and orientation time correlation at different structural regions of GQ DNA.The results show highly heterogeneous hydration patterns in both structure and dynamics;for example, there are several insular high-density sites in the inner channel, and ‘spine of water’ in the groove. For water inside the loop, anomalous diffusion is present over a long time scale, but for water around the phosphate group and groove, diffusion becomes normal after ~30 ps. These essentially correspond to deeply buried structural water and strong interaction with DNA, respectively.
基金Supported by the National Natural Science Foundation of China,No.81803773。
文摘Genomic instability and inflammation are considered to be two enabling characteristics that support cancer development and progression.G-quadruplex structure is a key element that contributes to genomic instability and inflammation.G-quadruplexes were once regarded as simply an obstacle that can block the transcription of oncogenes.A ligand targeting G-quadruplexes was found to have anticancer activity,making G-quadruplexes potential anticancer targets.However,further investigation has revealed that G-quadruplexes are widely distributed throughout the human genome and have many functions,such as regulating DNA replication,DNA repair,transcription,translation,epigenetics,and inflammatory response.G-quadruplexes play double regulatory roles in transcription and translation.In this review,we focus on G-quadruplexes as novel targets for the treatment of gastrointestinal cancers.We summarize the application basis of G-quadruplexes in gastrointestinal cancers,including their distribution sites,structural characteristics,and physiological functions.We describe the current status of applications for the treatment of esophageal cancer,pancreatic cancer,hepatocellular carcinoma,gastric cancer,colorectal cancer,and gastrointestinal stromal tumors,as well as the associated challenges.Finally,we review the prospective clinical applications of G-quadruplex targets,providing references for targeted treatment strategies in gastrointestinal cancers.
文摘使用含有偕胺肟基团的改性聚丙烯腈(PAN)纤维作为载体材料,通过轴向配位作用负载氯化血红素(hemin)制备了非均相催化剂hemin-PAN,重点对其在有机染料氧化降解反应中的催化性能进行研究。结果表明,hemin-PAN能够通过活化H2O2催化染料的氧化降解反应,其催化活性与纤维中偕胺肟基团数量密切相关,PAN增重率为14.9%时,hemin-PAN有最高的催化活性;增加催化剂hemin负载量或提高反应温度都有利于染料的氧化降解反应,hemin-PAN(增重率为14.9%,hemin负载量为0.026 mmol/g)催化罗丹明B染料氧化降解反应的活化能为63.83 k J/mol。
基金supported by the National Natural Science Foundation of China(Nos.21864026,21605130)the Natural Science Foundation of Yunnan Province,China(Nos.2018FB016,2016FD017).
文摘The insufficient internal resorption of iodide ions(I−)leads to thyroid disorders,such as goiter,hypothyroidism,and cretinism in adults.In this paper,a portable point-of-care testing(POCT)platform was developed for the dual-modal analysis of I^(−),seamlessly integrating both colorimetric and photothermal thermometer techniques.The quantification of results was achieved using a standard thermometer or smartphone.G-Quadruplex/Hemin(G4/Hemin)is the DNAzyme with peroxidase-like activity.The catalytic efficacy of G-quadruplex structures can be enhanced with the help of I^(−),manifesting as multicolor transitions from colorless to green and then blue,and accompanied by the increase of temperature,which can be used for the quantitative detection of I^(−).Additionally,digital analysis according to the three-color channels(R/G/B)by a cellphone eliminated the requirement for intricate instruments.This dual-modal method for portable I^(−)determination is cost-effectiveness,simplicity,remarkable sensitivity(0.5 nmol/L)and selectivity.Besides,it was applied to determining the concentration of I^(−)in spiked serum samples.
