Iridium Complex with Specific Intercalation in the G-Quadruplex: A Phosphorescence and Electrochemiluminescence Dual-Mode Homogeneous Biosensor for Enzyme-Free and Label-Free Detection of MicroRNA

ACS Sensors, Journal Year: 2023, Volume and Issue: 8(4), P. 1529 - 1535

Published: March 24, 2023

Design and exploitation of high-property multifunctional emitters for achieving immobilization-free, label-free, enzyme-free, dual-mode determination microRNA (miRNA) with high sensitivity selectivity are particularly urgent but remain a huge challenge. Herein, the first time, we reported an Ir3+-based N-heterocyclic complex, namely, IrPyPt, ascertained its phosphorescence electrochemiluminescence (ECL) dual-emission behavior in homogeneous solution, discovered turn-up signal-off ECL response to G-quadruplex DNA over other DNAs. Inspired by this, IrPyPt was pioneered as emitter combine nucleic acid probes (ON1 ON2) developing biosensor, which applied highly sensitive, credible analysis miRNA-21 used target analyte. triggered hybridization chain reaction ON1 ON2 generate abundant G-quadruplexes, caught yield IrPyPt@G-quadruplex, intramolecular rotary motion inhibited unable diffuse electrode, contributing boosted emission sharply declined emission. With this design, achieved limits detection down 1.40 0.18 pM, respectively. Furthermore, biosensor triumphantly determine concentration cancer cell lysates thus provided great potential alternative miRNA-related diseases' early accurate diagnosis.

Language: Английский

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Structural Insights into the Mechanism of High-Affinity Binding of Ochratoxin A by a DNA Aptamer

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(17), P. 7731 - 7740

Published: April 20, 2022

A 36-mer guanine (G)-rich DNA aptamer (OBA36) is able to distinguish one atomic difference between ochratoxin analogues (OTA) and B (OTB), showing prominent recognition specificity affinity among hundreds of aptamers for small molecules. Why OBA36 has >100-fold higher binding OTA than OTB remains a long-standing question due the lack high-resolution structure. Here we report solution NMR structure aptamer–OTA complex. It was found that induces fold into well-defined unique duplex–quadruplex structural scaffold stabilized by Mg2+ Na+ ions. does not directly interact with G-quadruplex, but specifically binds at junction double helix G-quadruplex through π–π stacking, halogen bonding (X-bond), hydrophobic interaction. same site as lacks X-bond. The strong X-bond formed chlorine atom aromatic ring C5 key discriminating toward OTA. present research contributes deeper insight molecular recognition, reveals basis high-affinity aptamers, provides foundation further engineering applications.

Language: Английский

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Harmonizing the growing fluorogenic RNA aptamer toolbox for RNA detection and imaging

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(12), P. 4071 - 4098

Published: Jan. 1, 2023

The field of fluorogenic RNA aptamers is a burgeoning research area that aims to address the lack naturally fluorescent molecules for detection and imaging.

Language: Английский

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Intricate 3D architecture of a DNA mimic of GFP

Nature, Journal Year: 2023, Volume and Issue: 618(7967), P. 1078 - 1084

Published: June 21, 2023

Language: Английский

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Comprehensive analysis of intramolecular G-quadruplex structures: furthering the understanding of their formalism

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(7), P. 3522 - 3546

Published: March 21, 2024

Abstract G-quadruplexes (G4) are helical structures found in guanine-rich DNA or RNA sequences. Generally, their formalism is based on a few dozen structures, which can produce some inconsistencies incompleteness. Using the website ASC-G4, we analyzed of 333 intramolecular G4s, all types, allowed us to clarify key concepts and present new information. To each eight distinguishable topologies corresponds groove-width signature predominant glycosidic configuration (gc) pattern governed by directions strands. The relative orientations stacking guanines within strands, quantified related vertical gc successions, determine twist tilt helices. latter impact minimum groove widths, represent space available for lateral ligand binding. G4 four helices have similar twists, even when these twists irregular, meaning that they various angles along Despite its importance, succession has no strict one-to-one relationship with topology, explains discrepancy between corresponding circular dichroism spectra. This study introduce concept platypus properties several topologies.

Language: Английский

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Recent Developments in G-Quadruplex Binding Ligands and Specific Beacons on Smart Fluorescent Sensor for Targeting Metal Ions and Biological Analytes

ACS Sensors, Journal Year: 2022, Volume and Issue: 7(10), P. 2833 - 2856

Published: Sept. 16, 2022

The G-quadruplex structure is crucial in several biological processes, including DNA replication, transcription, and genomic maintenance. G-quadruplex-based fluorescent probes have recently gained popularity because of their ease use, low cost, excellent selectivity, sensitivity. This review summarizes the latest applications structures as detectors genome-wide, enantioselective catalysts, disease therapeutics, promising drug targets, smart fluorescence probes. In every section, sensing employing G4 for detection other analytes were introduced, respectively. Since discovery structure, studies been conducted to investigate its conformations, potential, stability, reactivity, selectivity chemical modification, optical properties. formation mechanism advancements detecting different metal ions (Na+, K+, Ag+, Tl+, Cu+/Cu2+, Hg2+, Pb2+) biomolecules (AMP, ATP, DNA/RNA, microRNA, thrombin, T4 PNK, RNase H, ALP, CEA, lipocalin 1, UDG) using sensors based on such dye labels, artificial nucleobase moieties, complexes, intercalating dyes, bioconjugated nanomaterials (AgNCs, GO, QDs, CDs, MOF) described herein. To these extremely efficient responsive agents diagnostic therapeutic medicine, G-quadruplexes also employed a quantitative visualization technique.

Language: Английский

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RNA structure determination: From 2D to 3D

Fundamental Research, Journal Year: 2023, Volume and Issue: 3(5), P. 727 - 737

Published: June 12, 2023

RNA molecules serve a wide range of functions that are closely linked to their structures. The basic structural units consist single- and double-stranded regions. In order carry out advanced such as catalysis ligand binding, certain types RNAs can adopt higher-order analysis structures has progressed alongside advancements in biology techniques, but it comes with its own set challenges corresponding solutions. this review, we will discuss recent advances structure including probing methods, X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy, small-angle scattering. Often, combination multiple techniques is employed for the integrated We also survey important have been recently determined using various techniques.

Language: Английский

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Structure-based investigation of a DNA aptamer targeting PTK7 reveals an intricate 3D fold guiding functional optimization

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(29)

Published: July 10, 2024

DNA aptamers have emerged as novel molecular tools in disease theranostics owing to their high binding affinity and specificity for protein targets, which rely on ability fold into distinctive three-dimensional (3D) structures. However, delicate atomic interactions that shape the 3D structures are often ignored when designing modeling aptamers, leading inefficient functional optimization. Challenges persist determining high-resolution aptamer–protein complex Moreover, experimentally determined of molecules with exquisite functions remain scarce. These factors impede our comprehension optimization some important aptamers. Here, we performed a streamlined solution NMR-based structural investigation 41-nt sgc8c, prominent aptamer used target membrane tyrosine kinase 7, cancer theranostics. We show sgc8c prefolds an intricate three-way junction (3WJ) structure stabilized by long-range tertiary extensive base–base stackings. Delineated NMR chemical shift perturbations, site-directed mutagenesis, information, identified essential nucleotides constituting key elements centralized at core 3WJ. Leveraging well-established structure–function relationship, efficiently engineered two variants modifying apical loop introducing L -DNA base pairs simultaneously enhance thermostability, biostability, both cell feat not previously attained despite efforts. This work showcases simplified approach comprehend optimize without acquiring structure, offers principles sophisticated organization molecules.

Language: Английский

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Structure and mechanism of the methyltransferase ribozyme MTR1

Nature Chemical Biology, Journal Year: 2022, Volume and Issue: 18(5), P. 547 - 555

Published: March 17, 2022

Language: Английский

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A NIR fluorescent probe for imaging thiophenol in the living system and revealing thiophenol-induced oxidative stress

Chinese Chemical Letters, Journal Year: 2023, Volume and Issue: 34(8), P. 108507 - 108507

Published: April 28, 2023

Language: Английский

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