Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various de...Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic agents.Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the main reasons.Fortunately,many important structures of nucleic acids and their protein complexes have been determined over the past decade,which provide novel platforms for future drug design and discovery.In this review,we describe some useful nucleic acid structures,particularly their interactions with the ligands and therapeutic candidates or even drugs.We summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.展开更多
In this assay, a label-free fluorescent sensing platform based on triple-helix molecular switch（THMS） and G-quadruplex was developed for the detection of tetracycline. We demonstrated this approach by using THMS, wh...In this assay, a label-free fluorescent sensing platform based on triple-helix molecular switch（THMS） and G-quadruplex was developed for the detection of tetracycline. We demonstrated this approach by using THMS, which consists of a central section with a shortened 8-mer aptamer sequence with high affinity to tetracycline and flanked by two arm segments. G-rich oligonucleotide can specifically bind to thioflavin T（Th T） as a signal transduction probe（STP）. In the absence of tetracycline, THMS remains stable, the fluorescence of background is low. By the addition of target tetracycline, the aptamer-target binding results in the formation of a structured aptamer-target complex, which disassembles the THMS and releases the STP. The free STP self-assembles into G-quadruplex and specifically binds to Th T which generates a obvious fluorescence enhancement. Using the triple-helix molecular switch, the developed aptamer-based fluorescent sensing platform showed a linear relationship with the concentration of tetracycline ranging from 0.2 to 20.0 nmol/L. The detection limit of tetracycline was determined to be970.0 pmol/L. The assay avoids complicated modifications or chemical labeling, making it simple and cost-effective. So, it is expected that this aptamer-based fluorescent assay could be extensively applied in the field of food safety inspection.展开更多
G-quadruplex is a high-level structure composed of folded DNA or RNA rich in tandem repeats of guanine(G).In recent years,G-quadruplex is widely used in various fields due to its unique structural properties.This arti...G-quadruplex is a high-level structure composed of folded DNA or RNA rich in tandem repeats of guanine(G).In recent years,G-quadruplex is widely used in various fields due to its unique structural properties.This article briefly introduces the structural properties of G-quadruplex,and provides a brief introduction to the research on DNA and RNA G-quadruplex in various detection and medical fields.It is hoped that this can provide some help to readers who want to understand G-quadruplex.展开更多
基金financially supported by the Georgia Cancer Coalition(GCC) Distinguished Cancer Clinicians and Scientists and by the US National Science Foundation(NSF MCB-0824837)
文摘Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and antibiotics.Because of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic agents.Targeting nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the main reasons.Fortunately,many important structures of nucleic acids and their protein complexes have been determined over the past decade,which provide novel platforms for future drug design and discovery.In this review,we describe some useful nucleic acid structures,particularly their interactions with the ligands and therapeutic candidates or even drugs.We summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.
基金supported by National Natural Science Foundation of China (Nos. 21205142, 31370104)The Research Innovation Program for Graduates of Central South University (No. 2016zzts580)
文摘In this assay, a label-free fluorescent sensing platform based on triple-helix molecular switch（THMS） and G-quadruplex was developed for the detection of tetracycline. We demonstrated this approach by using THMS, which consists of a central section with a shortened 8-mer aptamer sequence with high affinity to tetracycline and flanked by two arm segments. G-rich oligonucleotide can specifically bind to thioflavin T（Th T） as a signal transduction probe（STP）. In the absence of tetracycline, THMS remains stable, the fluorescence of background is low. By the addition of target tetracycline, the aptamer-target binding results in the formation of a structured aptamer-target complex, which disassembles the THMS and releases the STP. The free STP self-assembles into G-quadruplex and specifically binds to Th T which generates a obvious fluorescence enhancement. Using the triple-helix molecular switch, the developed aptamer-based fluorescent sensing platform showed a linear relationship with the concentration of tetracycline ranging from 0.2 to 20.0 nmol/L. The detection limit of tetracycline was determined to be970.0 pmol/L. The assay avoids complicated modifications or chemical labeling, making it simple and cost-effective. So, it is expected that this aptamer-based fluorescent assay could be extensively applied in the field of food safety inspection.
基金supported by the National Natural Science Foundation of China(21864020,82160652)the Natural Science Foundation of Inner Mongolia(2019MS02014,2018MS02012)+2 种基金“Young Science and Technology Talents Program”(Leading Person)in Inner Mongolia Autonomous Region Colleges and Universities(NJYT-19-A04)Collaborative Innovation Center for Water Environmental Security of Inner Mongolia Autonomous Region,China(XTCX003)the Science and Technology Planning Project of Inner Mongolia Autonomous Region(2021GG0367).
文摘G-quadruplex is a high-level structure composed of folded DNA or RNA rich in tandem repeats of guanine(G).In recent years,G-quadruplex is widely used in various fields due to its unique structural properties.This article briefly introduces the structural properties of G-quadruplex,and provides a brief introduction to the research on DNA and RNA G-quadruplex in various detection and medical fields.It is hoped that this can provide some help to readers who want to understand G-quadruplex.
