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Unlocking g-quadruplexes as Targets and Tools against COVID-19

Chinese Journal of Chemistry 2023年第5期41卷 560-568页

作者： geng Qin Chuanqi Zhao jie Yang Zhao Wang Jinsong Ren Xiaogang Qu Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry ChineseAcademyof ScienceChangchunJilin 130022 University of Science and Technology of China HefeiAnhui 230026China

The applicability of g-quadruplexes(g4s)as antiviral targets,therapeutic agents and diagnostic tools for coronavirus disease 2019(COVID-19)is currently being evaluated,which has drawn the extensive attention of the scientific community.During the COVID-19 pandemic,research in this field is rapidly accumulating.In this review,we summarize the latest achievements and breakthroughs in the use of g4s as antiviral targets,therapeutic agents and diagnostic tools for COVID-19,particularly using g4 ligands.Finally,strength and weakness regarding g4s in anti-SARS-CoV-2 field are highlighted for prospective future projects.

关键词： g-quadruplexes Viruses Nucleic acids Drug discovery Aptamers

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Hierarchical Self-assembly of g-quadruplexes Based Hydrogel Consisting of guanine and Peptide Epitope

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中国化学:英文版 2023年第14期41卷 1727-1732页

作者： Hongyue Zhang Xuejiao Yang Juan Liang Kaihua Chen Huaimin Wang Department of Chemistry Zhejiang UniversityHangzhouZhejiang310027 China Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province Department of ChemistrySchool of ScienceWestlake UniversityInstitute of Natural SciencesWestlake Institute for Advanced StudyNo.600 Dunyu RoadHangzhouZhejiang310024 China

guanosine-based hydrogels have attracted considerable attention because of their simplicity and easy preparation.However,the sugar moiety limits its further applications because of the necessity of sugar in the hydrogel formation.This work reports a g-quadruplexes-based hydrogel consisting of guanine and peptide epitope to form a supramolecular hydrogel in the presence of metal cations.Using the metal ion-responsive peptide epitope from the ion channel to replace sugar motif at N9 position of guanosine results in a novel nucleopeptide.The results show that the gelation time,the diameter of nanofibers,the anisotropic property,and the mechanical property of the hydrogel can be simply controlled using metal cations.The magnesium and calcium ions direct the alignment of nanofibers to form anisotropic nano-bundles.The mechanistic studies indicate the formation of g-quadruplexes in the hydrogel.Compared to the storage modulus of nucleopeptide without the metal cation,adding zinc ions results in an over three-order increase in mechanical properties.Cytotoxicity experiment indicates the good biocompatibility of our hydrogel.Moreover,we demonstrate that the guanine-capped peptide could release STINg agonist in a controlled manner.This work illustrates a simple way to modulate the property of the nucleopeptide hydrogel to develop soft materials.

关键词： g-quadruplexes Peptides Nucleobases Self-assembly Hydrogels Cell culture

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Interaction between human telomeric g-quadruplexes characterized by single molecule magnetic tweezers

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Chinese Physics B 2018年第6期27卷 543-553页

作者：王一舟侯锡苗车海鹏肖雪奚绪光窦硕星王鹏业李伟 Key Laboratory of Soft Matter Physics Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of Sciences School of Physical Sciences University of Chinese Academy of Sciences School of Life Sciences Northwest A & F University

Human telomeric g-quadruplex plays a crucial role in regulating the genome stability. Despite extensive studies on structures and kinetics of monomeric g-quadruplex, the interaction between g-quadruplexes is still in debate. In this work,we employ magnetic tweezers to investigate the folding and unfolding kinetics of two contiguous g-quadruplexes in 100-mM K~＋buffer. The interaction between g-quadruplexes and the consequent effect on the kinetics of g-quadruplex are revealed. The linker sequence between g-quadruplexes is further found to play an important role in the interaction between two g-quadruplexes. Our results provide a high-resolution insight into kinetics of multimeric g-quadruplexes and genome stability.

关键词： biophysics g-quadruplexes single-molecule studies DNA structures

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Bloom's syndrome protein unfolding g-quadruplexes in two pathways

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Chinese Physics B 2017年第8期26卷 561-564页

作者：赵振业徐春华史婧李菁华马建兵贾棋马东飞李明陆颖 Key Laboratory of Soft Matter Physics.Institute of Physics Chinese Academy of SciencesBeijing 100190China Beijing National Laboratory for Condensed Matter Physics Institute of Physics and School of Physical SciencesUniversity of Chinese Academy of SciencesBeijing 100190China College of Lit'e Science Northwest A&F UniversityXianyang 712100China Material and Energy School Guangdong University of Technology.Guangzhou 510006China

The Bloom helicase （BLM） gene product encodes a DNA helicase that functions in homologous recombination repair to prevent genomic instability. BLM is highly active in binding and unfolding g-quadruplexes （g4）, which are non- canonical DNA structures formed by Hoogsteen base-pairing in guanine-rich sequences. Here we use single-molecule fluorescence resonance energy transfer （smFRET） to study the molecular mechanism of BLM-catalysed g4 unfolding and show that BLM unfolds g4 in two pathways. Our data enable us to propose a model in which the HRDC domain functions as a regulator of BLM, depending on the position of the HRDC domain of BLM in action： when HRDC binds to the g4 sequence, BLM may hold g4 in the unfolded state; otherwise, it may remain on the unfolded g4 transiently so that g4 can refold immediately.

关键词： g-quadruplexes BLM helicase smFRET

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A DNA g-quadruplex converts SOD1 into fibrillar aggregates

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Chinese Chemical Letters 2021年第7期32卷 2322-2326页

作者： Wenqian Liu Yulin Xu Xue Li Yan Meng Huiling Wang Chunrong Liu Changlin Liu Li Wang Key Laboratory of Pesticide&Chemical Biology Ministry of Educationand School of ChemistryCentral China Normal UniversityWuhan 430079China Wuhan No.1 Huiquan Middle School Wuhan 430022China

Nucleic acids with g4 elements play a role in the formation of aggregates involved in intracellular phase transitions.Our previous studies suggest that different forms of DNA could act as an accelerating template in Cu/Zn superoxide dismutase(SOD1)aggregation.Here,we examined the regulation of fo rmation and cytotoxicity of the SOD1 aggregates by single-stranded 12-merdeoxynucleotide oligomers(dN)_(12)(N=A,T,g,C;ssDNAs)under acidic conditions.The ssDNAs can be divided into two groups based on their roles in SOD1 binding,exposure of hydrophobic clusters in SOD1,accelerated formation,morphology and cytotoxicity of SOD1 aggregates.g-quadruplexes convert SOD1 into fibrillar aggregates as a template,a fact which was observed for the first time in the nucleic acid regulation of protein aggregation.Moreover,the fibrillar or fibril-like SOD1 species with a g-quadruplex provided by(dg)_(12)were less toxic than the amorphous species with(dN)_(12)(N=A,T).This study not only indicates that both morphology and cytotoxicity of protein aggregates can be regulated by the protein-bound DNAs,but also help us understand roles of nucleic aid g-quadruplexes in the formation of aggregates and membrane less organelles involved in intracellular phase transitions.

关键词： SOD1 Deoxynucleotide oligomers(dN)_(12) g-quadruplexes Fibrillar aggregates

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