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Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution
Published on: August 16, 2016
Single-Molecule Discrimination of Multisialylated Ganglioside Oligosaccharides Using an Engineered Nanopore
Guangda Yao1, Boyang Ren1,2, Daigui Zhu3,4
1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Research (Washington, D.C.)
|May 21, 2026
Summary
We developed a nanopore sensing strategy to identify individual ganglioside oligosaccharides. This method distinguishes complex structures, including isomers, by analyzing their unique dynamic signatures within the nanopore.
Area of Science:
- Biochemistry
- Nanotechnology
- Analytical Chemistry
Background:
- Ganglioside oligosaccharides are crucial for biological functions.
- Their structural complexity, especially sialic acid arrangement, poses identification challenges.
- Current methods struggle with high charge density and subtle isomeric differences.
Purpose of the Study:
- To develop a single-molecule nanopore strategy for identifying ganglioside oligosaccharides.
- To overcome limitations in discriminating highly sialylated and isomeric glycans.
- To enable glycan sequence elucidation in complex biological samples.
Main Methods:
- Engineered an α-hemolysin nanopore with cationic and aromatic mutations.
- Utilized synergistic mutations to enhance glycan capture and pore residence time.
- Analyzed intraevent current fluctuations using time- and spectral-domain features.
Main Results:
- Successfully discriminated 4 linkage isomers of trisialylated ganglioside glycans.
- Accurately identified ganglioside oligosaccharides with 3-5 sialic acid residues in mixtures.
- Achieved single-level isomer identification and mixture deconvolution using machine learning.
Conclusions:
- Controlled analyte-pore interactions unlock higher-order dynamical signatures for nanopore analysis.
- This strategy enables the analysis of highly sialylated ganglioside oligosaccharides.
- Provides a general approach for single-molecule glycan sequence elucidation in biological contexts.
