Glycosaminoglycans: What Remains To Be Deciphered?

JACS Au, Journal Year: 2023, Volume and Issue: 3(3), P. 628 - 656

Published: March 2, 2023

Glycosaminoglycans (GAGs) are complex polysaccharides exhibiting a vast structural diversity and fulfilling various functions mediated by thousands of interactions in the extracellular matrix, at cell surface, within cells where they have been detected nucleus. It is known that chemical groups attached to GAGs GAG conformations comprise "glycocodes" not yet fully deciphered. The molecular context also matters for structures functions, influence structure proteoglycan core proteins on sulfated vice versa warrants further investigation. lack dedicated bioinformatic tools mining data sets contributes partial characterization functional landscape GAGs. These pending issues will benefit from development new approaches reviewed here, namely (i) synthesis oligosaccharides build large diverse libraries, (ii) analysis sequencing mass spectrometry (e.g., ion mobility-mass spectrometry), gas-phase infrared spectroscopy, recognition tunnelling nanopores, modeling identify bioactive sequences, biophysical methods investigate binding interfaces, expand our knowledge understanding glycocodes governing recognition, (iii) artificial intelligence in-depth investigation GAGomic their integration with proteomics.

Language: Английский

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Decoding the glycoproteome: a new frontier for biomarker discovery in cancer

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: March 22, 2024

Abstract Cancer early detection and treatment response prediction continue to pose significant challenges. liquid biopsies focusing on detecting circulating tumor cells (CTCs) DNA (ctDNA) have shown enormous potential due their non-invasive nature the implications in precision cancer management. Recently, biopsy has been further expanded profile glycoproteins, which are products of post-translational modifications proteins play key roles both normal pathological processes, including cancers. The advancements chemical mass spectrometry-based technologies artificial intelligence-based platforms enabled extensive studies organ-specific changes glycans glycoproteins through glycomics glycoproteomics. Glycoproteomic analysis emerged as a promising tool for biomarker discovery development cancers efficacy immunotherapies. These biomarkers could crucial role aiding intervention personalized therapy decisions. In this review, we summarize advance glycoproteomic promise challenges integration into clinical practice improve patient care.

Language: Английский

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Avian and Human Influenza A Virus Receptors in Bovine Mammary Gland

Emerging infectious diseases, Journal Year: 2024, Volume and Issue: 30(9)

Published: Aug. 23, 2024

An outbreak of influenza A (H5N1) virus was detected in dairy cows the United States. We sialic acid -α2,3/α2,6-galactose host receptors bovine mammary glands by lectin histochemistry. Our results provide a rationale for high levels H5N1 milk from infected cows.

Language: Английский

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The avian and human influenza A virus receptors sialic acid (SA)-α2,3 and SA-α2,6 are widely expressed in the bovine mammary gland

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 3, 2024

Abstract An outbreak of H5N1 highly pathogenic influenza A virus (HPIAV) has been detected in dairy cows the United States. Influenza (IAV) is a negative-sense, single-stranded, RNA that not previously associated with widespread infection cattle. As such, cattle are an extremely under-studied domestic IAV host species. receptors on cells sialic acids (SAs) bound to galactose either α2,3 or α2,6 linkage. Human IAVs preferentially bind SA-α2,6 (human receptor), whereas avian have preference for (avian receptor). The receptor can further be divided into two receptors: isolated from chickens generally more tightly SA-α2,3-Gal-β1,4 (chicken duck SA-α2,3-Gal-β1,3 (duck We found all were expressed, different degree, mammary gland, respiratory tract, and cerebrum beef and/or human widely expressed bovine chicken dominated tract. In general, only low expression was observed neurons cerebrum. These results provide mechanistic rationale high levels reported infected milk show potential act as mixing vessel novel generation. Graphical abstract Created Biorender.com

Language: Английский

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Genetics of glycosylation in mammalian development and disease

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: May 9, 2024

Language: Английский

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Mutant glycosidases for labeling sialoglycans with high specificity and affinity

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Affinity labeling of biomacromolecules is vital for bioimaging and functional studies. However, affinity probes recognizing glycans with high specificity remain scarce. Here we report the development glycan recombinant binders (GRABs) based on mutant bacterial sialidases, which are enzymatically inactive but preserve stringent sialoglycan substrates. By mutating a key catalytic residue Streptococcus pneumoniae neuraminidase A (SpNanA) Ruminococcus gnavus H (RgNanH), develop GRAB-Sia GRAB-Sia3 total sialoglycans α2,3-sialosides, respectively. The GRABs exhibit strict substrate linkage specificity, tetramerization streptavidin substantially increases their avidity. tetrameric (tetra-GRABs) effective tools probing in immunoblotting, flow cytometry, immunoprecipitation, fluorescence imaging. Furthermore, multiplex analysis tetra-GRABs uncovers spatially distinct various mouse organs. This work provides versatile toolkit analyzing sensitivity, convenience. Highly specific labels scarce, limiting use many applications. Here, authors sialidase mutants, sialoglycans.

Language: Английский

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Glycoinformatics in the Artificial Intelligence Era

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(20), P. 15971 - 15988

Published: Aug. 12, 2022

Artificial intelligence (AI) methods have been and are now being increasingly integrated in prediction software implemented bioinformatics its glycoscience branch known as glycoinformatics. AI techniques evolved the past decades, their applications not yet widespread. This limited use is partly explained by peculiarities of glyco-data that notoriously hard to produce analyze. Nonetheless, time goes, accumulation glycomics, glycoproteomics, glycan-binding data has reached a point where even most recent deep learning can provide predictors with good performance. We discuss historical development application various broader field A particular focus placed on shining light challenges handling, contextualized lessons learnt from related disciplines. Ending discussion state-of-the-art approaches glycoinformatics, we also envision future including need occur order truly unleash capabilities systems biology era.

Language: Английский

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Tools for mammalian glycoscience research

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2657 - 2677

Published: July 1, 2022

Language: Английский

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ST6GAL1‐mediated aberrant sialylation promotes prostate cancer progression

The Journal of Pathology, Journal Year: 2023, Volume and Issue: 261(1), P. 71 - 84

Published: Aug. 7, 2023

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every type. A common change tumour cell an increase α2,6 sialylation N-glycans, modification driven by the sialyltransferase ST6GAL1. ST6GAL1 overexpressed numerous types, sialylated are fundamental for growth, metastasis, immune evasion, drug resistance, but role prostate poorly understood. Here, we analyse matched normal tissue samples from 200 patients verify that upregulated tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), identify larger branched N-glycans show specificity to We also monitored plasma >400 reveal levels significantly increased blood men with cancer. both vitro vivo studies, demonstrate promotes growth invasion. Our findings introduces on cells raise possibility can secrete active enzyme capable remodelling surface other cells. Furthermore, find expressed be targeted using inhibitor P-3FAX -Neu5Ac. study identifies important progression highlights opportunity inhibit abnormal development new therapeutics. © 2023 The Authors. Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.

Language: Английский

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Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone

EBioMedicine, Journal Year: 2024, Volume and Issue: 104, P. 105163 - 105163

Published: May 20, 2024

Language: Английский

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