Probing Nanopores: Molecular Dynamics Insights into the Mechanisms of DNA and Protein Translocation through Solid-State and Biological Nanopores

Soft Matter, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Nanopore sequencing technology has revolutionized single-molecule analysis through its unique capability to detect and characterize individual biomolecules with unprecedented precision.

Язык: Английский

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Single-Molecule Identification and Quantification of Steviol Glycosides with a Deep Learning-Powered Nanopore Sensor

ACS Nano, Год журнала: 2024, Номер 18(36), С. 25155 - 25169

Опубликована: Авг. 27, 2024

Steviol glycosides (SGs) are a class of high-potency noncalorie natural sweeteners made up common diterpenoid core and varying glycans. Thus, the diversity glycans in composition, linkage, isomerism results tremendous structural complexity SG family, which poses challenges for precise identification leads to fact that SGs frequently used mixtures their variances biological activity remain largely unexplored. Here we show wild-type aerolysin nanopore can detect discriminate diverse species through modulable electro-osmotic flow effect at varied applied voltages. At low voltages, neutral molecule was drawn stuck pore entrance due an energy barrier around R220 sites. The ensuing binding events enable majority species. Increasing voltage break cause translocation events, allowing unambiguous several pairs differing by only one hydroxyl group recognition accumulation from multiple sensing regions Based on data 15 SGs, deep learning-based artificial intelligence (AI) model created process individual blockage achieving rapid, automated, single-molecule quantification real samples. This work highlights value analysis complex glycans-containing glycosides, as well potential sensitive rapid quality assurance glycoside products with use AI.

Язык: Английский

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Recent Progress in Chemoenzymatic Synthesis of Human Glycans

Organic & Biomolecular Chemistry, Год журнала: 2024, Номер 22(38), С. 7767 - 7785

Опубликована: Янв. 1, 2024

Glycan is an essential cell component that usually exists in either a free form or glycoconjugated form. Glycosylation affects the regulatory function of glycoconjugates health and disease development, indicating key role glycan organisms. Because complexity diversity structures, it challenging to prepare structurally well-defined glycans, which hinders investigation biological functions at molecular level. Chemoenzymatic synthesis attractive approach for preparing complex because avoids tedious protecting group manipulations chemical ensures high regio- stereo-selectivity glucosides during assembly. Herein, enzymes, such as glycosyltransferases (GTs) glycosidases (GHs), sugar donors involved chemoenzymatic human glycans are initially discussed. Many state-of-the-art methodologies subsequently displayed summarized illustrate development synthetic example,

Язык: Английский

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Glycan Sequencing Based on Glycosidase-Assisted Nanopore Sensing

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Nanopores are promising sensors for glycan analysis with the accurate identification of complex glycans laying foundation nanopore-based sequencing. However, their applicability toward continuous sequencing has not yet been demonstrated. Here, we present a proof-of-concept by combining nanopore technology glycosidase-hydrolyzing reactions. By continuously monitoring changes in characteristic current generated translocation hydrolysis products through nanopore, sequence can be accurately identified based on specificity glycosidases. With machine learning, improved accuracy to over 98%, allowing reliable determination consecutive building blocks and glycosidic linkages chains while reducing need operator expertise. This approach was validated real samples, calibrated using hydrophilic interaction chromatography-high-performance liquid chromatography (HILIC-HPLC) mass spectrometry (MS). We achieved ten units natural chains, which provided first evidence feasibility nanopore-glycosidase-compatible system Compared traditional methods, this strategy enhances efficiency 5-fold. Additionally, introduced concept 'inverse sequencing', focuses electrical signal rather than monosaccharide identification. eliminates reliance fingerprint libraries typically required putative 'forward hydrolysis' strategies. When challenges both inverse strategies' addressed, will pave way establishing at single-molecule level.

Язык: Английский

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Single-molecule resolution of the conformation of polymers and dendrimers with solid-state nanopores

Talanta, Год журнала: 2025, Номер 286, С. 127544 - 127544

Опубликована: Янв. 10, 2025

Язык: Английский

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The Road Toward Nanopore Sequencing of Glycosaminoglycans

Handbook of experimental pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Research Progress on Saccharide Molecule Detection Based on Nanopores

Sensors, Год журнала: 2024, Номер 24(16), С. 5442 - 5442

Опубликована: Авг. 22, 2024

Saccharides, being one of the fundamental molecules life, play essential roles in physiological and pathological functions cells. However, their intricate structures pose challenges for detection. Nanopore technology, with its high sensitivity capability single-molecule-level analysis, has revolutionized identification structural analysis saccharide molecules. This review focuses on recent advancements nanopore technology carbohydrate detection, presenting an array methods that leverage molecular complexity saccharides. Biological techniques utilize specific protein binding or pore modifications to trigger typical resistive pulses, enabling high-sensitivity detection monosaccharides oligosaccharides. In solid-state sensing, boronic acid modification pH gating mechanisms are employed recognition quantitative polysaccharides. The integration artificial intelligence algorithms can further enhance accuracy reliability analyses. Serving as a crucial tool we foresee significant potential application disease diagnosis, drug screening, biosensing, fostering innovative progress related research domains.

Язык: Английский

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Unraveling Clinical Glycoproteome by Integrating Affinity Enrichment with Nanopore Sequencing

ChemBioChem, Год журнала: 2024, Номер unknown

Опубликована: Сен. 5, 2024

Abstract This prospect explores the integration of enrichment strategies with nanopore detection to advance clinical glycoproteomics. Glycoproteins, crucial for understanding biological processes, pose challenges due their low abundance and structural diversity. Enrichment techniques using lectin affinity, boronate hydrazide chemistry especially molecular imprinted polymers may selectively specifically isolate glycoproteins from complex samples, while technology enables label‐free, real‐time, single‐molecule analysis. approach holds promise disease‐related glycosylation studies, biomarker discovery, personalized medicine, streamlined Standardization, optimization, data analysis remain challenges, requiring interdisciplinary collaborations technological advancements. Overall, this offer transformative potential glycoproteomics innovative diagnostic therapeutic strategies.

Язык: Английский

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Nanopore Identification of Polyglutamine Length via Cross-Slit Sensing

The Journal of Physical Chemistry Letters, Год журнала: 2024, Номер unknown, С. 11792 - 11800

Опубликована: Ноя. 18, 2024

Nanopore sensing is now reshaping analytical proteomics with its simplicity, convenience, and high sensitivity. Determining the length of polyglutamine (polyQ) crucial for rapid screening Huntington's disease. In this computational study, we present a cross-nanoslit detection approach to determine polyQ length, where nanoslit carved within two-dimensional (2D) in-plane heterostructure graphene (GRA) hexagonal boron nitride (hBN). We designed an hBN strip embedded in sheet. With such design, peptides can spontaneously linearly stretch out on stripe. By tuning strength external electric field, molecular transportation along stripe be effectively regulated. Subsequent motion applied record time-dependent signals. The signal features are then utilized train machine learning classification models. machine-learning-assisted recognition enables accurate determination protein's length. This nanoslit-sensing method may offer theoretical guidance 2D design peptide lengths protein-related diseases.

Язык: Английский

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Azo-PMA Nanopores of Sub-20 nm Length for Unimolecular Resolution of Nucleic Acids and Proteins

Talanta, Год журнала: 2024, Номер 285, С. 127402 - 127402

Опубликована: Дек. 16, 2024

Язык: Английский

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