Protein glycosylation and glycoinformatics for novel biomarker discovery in neurodegenerative diseases

Costa, Júlia; Hayes, Catherine A.; Lisacek, Frédérique

doi:10.1016/j.arr.2023.101991

Cited by 8 publications

(6 citation statements)

References 201 publications

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“…The current techniques for glycoprotein analysis require tedious sample preparation, including enzymatically releasing glycans from glycoproteins and chemically labeling glycans for detection. − For example, the glycosidase (PNGase F/PNGase A) could be used to cleave the N -glycans from glycoproteins, and then the glycans are purified via hydrophilic interaction liquid chromatography. , According to the detection techniques, chemical labeling of the glycans may be required for liquid chromatography (LC) or LC-MS. , For the O -glycan analysis, the procedure can be more complicated due to the lack of enzymatic cleavage methods. While chemical release approaches exist, there is a risk of glycan structure degradation during the release process .…”

Section: Resultsmentioning

confidence: 99%

Direct Glycan Analysis of Biological Samples and Intact Glycoproteins by Integrating Machine Learning-Driven Surface-Enhanced Raman Scattering and Boronic Acid Arrays

Hu,

2024

ACS Meas. Sci. Au

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Frequent monitoring of glycan patterns is a critical step in studying glycan-mediated cellular processes. However, the current glycan analysis tools are resource-intensive and less suitable for routine use in standard laboratories. We developed a novel glycan detection platform by integrating surface-enhanced Raman spectroscopy (SERS), boronic acid (BA) receptors, and machine learning tools. This sensor monitors the molecular fingerprint spectra of BA binding to cis-diol-containing glycans. Different types of BA receptors could yield different stereoselective reactions toward different glycans and exhibit unique vibrational spectra. By integration of the Raman spectra collected from different BA receptors, the structural information can be enriched, eventually improving the accuracy of glycan classification and quantification. Here, we established a SERS-based sensor incorporating multiple different BA receptors. This sensing platform could directly analyze the biological samples, including whole milk and intact glycoproteins (fetuin and asialofetuin), without tedious glycan release and purification steps. The results demonstrate the platform’s ability to classify milk oligosaccharides with remarkable classification accuracy, despite the presence of other non-glycan constituents in the background. This sensor could also directly quantify sialylation levels of a fetuin/asialofetuin mixture without glycan release procedures. Moreover, by selecting appropriate BA receptors, the sensor exhibits an excellent performance of differentiating between α2,3 and α2,6 linkages of sialic acids. This low-cost, rapid, and highly accessible sensor will provide the scientific community with an invaluable tool for routine glycan screening in standard laboratories.

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Section: Resultsmentioning

confidence: 99%

Direct Glycan Analysis of Biological Samples and Intact Glycoproteins by Integrating Machine Learning-Driven Surface-Enhanced Raman Scattering and Boronic Acid Arrays

Hu,

2024

ACS Meas. Sci. Au

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“…In this context, recent evidence indicated that GLT8D1 was relevant in ganglioside biosynthesis 16 . Glycoproteins could also constitute potential substrates; for example, the T-antigen and related structures are present in mucins with important roles in cancer 44 and sialylated T-antigen is abundantly expressed in brain tissue glycoproteins [45][46][47] , but the enzymes involved in their biosynthesis have been well-studied. On the other hand, core 8 is a low abundance structure in glycoproteins from brain tissue 46,48 with unknown functional relevance, and GLT8D1 appears to have www.nature.com/scientificreports/ the capacity to synthesize that structure.…”

Section: Discussionmentioning

confidence: 99%

Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) is a UDP-dependent galactosyltransferase

Vicente,

Guerreiro,

Felgueiras

et al. 2023

Sci Rep

Self Cite

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Glycosyltransferases (GTs) are enzymes that catalyze the formation of glycosidic bonds and hundreds of GTs have been identified so far in humans. Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) has been associated with central nervous system diseases and cancer. However, evidence on its enzymatic properties, including its substrates, has been scarcely described. In this paper, we have produced and purified recombinant secretory GLT8D1. The enzyme was found to be N-glycosylated. Differential scanning fluorimetry was employed to analyze the stabilization of GLT8D1 by Mn2+ and nucleotides, revealing UDP as the most stabilizing nucleotide scaffold. GLT8D1 displayed glycosyltransferase activity from UDP-galactose onto N-acetylgalactosamine but with a low efficiency. Modeling of the structure revealed similarities with other GT-A fold enzymes in CAZy family GT8 and glycosyltransferases in other families with galactosyl-, glucosyl-, and xylosyltransferase activities, each with retaining catalytic mechanisms. Our study provides novel structural and functional insights into the properties of GLT8D1 with implications in pathological processes.

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Section: Direct Analysis Of Intact Glycoproteinsmentioning

confidence: 99%

“…In addition, we used this platform to directly analyze intact glycoproteins. Protein glycosylation analysis typically requires tedious sample preparation, such as enzymatically releasing glycans from glycoproteins and chemically labeling glycans for detection [21][22][23] . Direct analysis of intact glycoproteins will speed up the analysis procedure and benefit the glycobiology community.…”

Section: Introductionmentioning

confidence: 99%

Direct Glycan Analysis of Biological Samples and Intact Glycoproteins by Integrating Machine Learning Driven- Surface-Enhanced Raman Scattering (SERS) and Boronic Acid Array

Hu,

2024

Preprint

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Frequent monitoring of glycan patterns is a critical step for studying glycan-mediated cellular processes. However, the current glycan analysis tools are resource-intensive and less suitable for routine use in standard laboratories. We developed a novel glycan detection platform by integrating surface-enhanced Raman spectroscopy (SERS), boronic acid (BA) receptors, and machine learning (ML) tools. This sensor monitors the molecular fingerprint spectra of BA binding to cis-diol-containing glycans. Different types of BA could yield different stereoselective reactions toward different glycans and exhibit unique vibrational spectra. By integrating the Raman spectra collected from different BA receptors, the structural information can be enriched, eventually improving the accuracy of glycan classification and quantification. Here, we established a SERS-based sensor incorporating multiple different BA receptors. This sensing platform could directly analyze the biological samples, including the whole milk and intact glycoproteins (fetuin and asialofetuin), without tedious glycan release and purification steps. The results demonstrate the platform's ability to classify milk oligosaccharides with remarkable classification accuracy, despite the presence of other non-glycan constituents in the background. This sensor could also directly quantify sialylation levels of fetuin/asialofetuin mixture without glycan release procedures. Moreover, by selecting appropriate BA receptors, the sensor exhibits an excellent performance of differentiating between α2,3 and α2,6 linkages of sialic acids. This low-cost, rapid, and highly accessible sensor will provide the scientific community with an invaluable tool for routine glycan screening in standard laboratories.

show abstract

Protein glycosylation and glycoinformatics for novel biomarker discovery in neurodegenerative diseases

Cited by 8 publications

References 201 publications

Direct Glycan Analysis of Biological Samples and Intact Glycoproteins by Integrating Machine Learning-Driven Surface-Enhanced Raman Scattering and Boronic Acid Arrays

Direct Glycan Analysis of Biological Samples and Intact Glycoproteins by Integrating Machine Learning-Driven Surface-Enhanced Raman Scattering and Boronic Acid Arrays

Glycosyltransferase 8 domain-containing protein 1 (GLT8D1) is a UDP-dependent galactosyltransferase

Direct Glycan Analysis of Biological Samples and Intact Glycoproteins by Integrating Machine Learning Driven- Surface-Enhanced Raman Scattering (SERS) and Boronic Acid Array

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