Probing Sialidases or Siglecs with Sialic Acid Analogues, Clusters and Precursors

Liu, Guangjian; Jia, Liyan; Xing, Guo‐wen

doi:10.1002/ajoc.201900618

Cited by 5 publications

(7 citation statements)

References 72 publications

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“…Further examples of sialic acid analogues as probes of sialidases and Siglecs were reported in 2020 by Liu et al, including sialic acid clusters with high affinity for Siglecs, as well as fluorophore-labelled sialic acid analogues for imaging cell-surface sialylation. 197 …”

Section: Targeting Sialic-based Interactions Of Siglecs Selectins and Galectinsmentioning

confidence: 99%

Insights into the role of sialylation in cancer progression and metastasis

2020

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Upregulation of sialyltransferases—the enzymes responsible for the addition of sialic acid to growing glycoconjugate chains—and the resultant hypersialylation of up to 40–60% of tumour cell surfaces are established hallmarks of several cancers, including lung, breast, ovarian, pancreatic and prostate cancer. Hypersialylation promotes tumour metastasis by several routes, including enhancing immune evasion and tumour cell survival, and stimulating tumour invasion and migration. The critical role of enzymes that regulate sialic acid in tumour cell growth and metastasis points towards targeting sialylation as a potential new anti-metastatic cancer treatment strategy. Herein, we explore insights into the mechanisms by which hypersialylation plays a role in promoting metastasis, and explore the current state of sialyltransferase inhibitor development.

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Section: Targeting Sialic-based Interactions Of Siglecs Selectins and Galectinsmentioning

confidence: 99%

Insights into the role of sialylation in cancer progression and metastasis

2020

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“…The role of fucosylation in cell migration may be explained much more simply. Defucosylation inhibits cell migration, whereas FUT8 deficiency suppresses cell migration by impacting the core fucosylation of E-cadherin and the downstream FAK/ integrin pathway (Chen et al, 2013;Isaji et al, 2006;Liu et al, 2020). Reversely, upregulated fucosylation through FUT1,2,3,6 and 8 increases cell migration and is associated with poor prognosis in non-small cell lung cancer (Park et al, 2020) and hepatoma (Wu and Chen, 2009).…”

Section: Discussionmentioning

confidence: 99%

The role of altered glycosylation in human nucleus pulposus cells in inflammation and degeneration

Joyce¹,

Isa²,

Krouwels³

et al. 2021

eCM

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Intervertebral disc (IVD) degeneration causes low-back pain through disc compression, prolapse and herniation. Inflammation of the IVD and subsequent degeneration produce altered glycosylation profiles in several animal models of IVD injury and ageing, although the function of this altered glycosylation pattern in a human is unknown. Altered N-glycome, specifically sialylated and fucosylated N-glycosylation motif expression, might play a role in inflammation and disease progression. Healthy (foetal and adolescent idiopathic scoliosis) and degenerated (lumbar degeneration) human IVD glycosylation patterns were studied using lectin histochemistry. Small-molecule fluorinated sugar analogues (3Fax-Peracetyl Neu5Ac; 2F-Peracetyl-Fucose) were used to inhibit sialylation and fucosylation in an in vitro model of inflammation, to investigate their effects on the glycosignature, cell metabolism, extracellular matrix synthesis and cell migration. The effects of interleukin (IL)-1β, tumour necrosis factor (TNF)-α and IL-6 on glycosylation in human nucleus pulposus cells were investigated by lectin histochemistry, PCR and enzyme-linked immunosorbent assay (ELISA). In the in vitro model of IVD degeneration, cytokine-induced inflammation-induced hypersialylation was observed, as indicated by Sambucus nigra I binding. However, this modification was inhibited by the sialyltransferase inhibitor. Inhibition of sialylation and fucosylation modulates cell migration and protein translation of catabolic enzymes in response to inflammation. The altered patterns of glycosylation in human tissue in degeneration was consistent with previous IVD studies in murine, bovine and ovine models. The present study was the first functional investigation of glycosylation in human degenerated IVD, elucidating the role of the glycome in disease progression and identified potential therapeutic targets for future regenerative therapies.

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“…For example, tumor cells can utilize sialoglycan–Siglec interactions to modulate immune cell function by promoting the creation of the immunosuppressive tumor microenvironment. In this regard, multivalent scaffolds, including liposomes, polymers/polysaccharides, VLPs, and other nanoparticles, have been exploited to target Siglecs with high affinity, improving or alleviating immune response via sialoglycan–Siglec interaction. − A series of studies has been reported by the Paulson and other groups, with detailed information (e.g., chemical structures of ligands for every Siglec) provided in the previous reviews. , Some representative polymeric glycomaterials for modulation of the immune response are highlighted below.…”

Section: Immunologymentioning

confidence: 99%

Carbohydrate-Based Macromolecular Biomaterials

et al. 2021

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Carbohydrates are the most abundant and one of the most important biomacromolecules in Nature. Except for energy-related compounds, carbohydrates can be roughly divided into two categories: Carbohydrates as matter and carbohydrates as information. As matter, carbohydrates are abundantly present in the extracellular matrix of animals and cell walls of various plants, bacteria, fungi, etc., serving as scaffolds. Some commonly found polysaccharides are featured as biocompatible materials with controllable rigidity and functionality, forming polymeric biomaterials which are widely used in drug delivery, tissue engineering, etc. As information, carbohydrates are usually referred to the glycans from glycoproteins, glycolipids, and proteoglycans, which bind to proteins or other carbohydrates, thereby meditating the cell–cell and cell–matrix interactions. These glycans could be simplified as synthetic glycopolymers, glycolipids, and glycoproteins, which could be afforded through polymerization, multistep synthesis, or a semisynthetic strategy. The information role of carbohydrates can be demonstrated not only as targeting reagents but also as immune antigens and adjuvants. The latter are also included in this review as they are always in a macromolecular formulation. In this review, we intend to provide a relatively comprehensive summary of carbohydrate-based macromolecular biomaterials since 2010 while emphasizing the fundamental understanding to guide the rational design of biomaterials. Carbohydrate-based macromolecules on the basis of their resources and chemical structures will be discussed, including naturally occurring polysaccharides, naturally derived synthetic polysaccharides, glycopolymers/glycodendrimers, supramolecular glycopolymers, and synthetic glycolipids/glycoproteins. Multiscale structure–function relationships in several major application areas, including delivery systems, tissue engineering, and immunology, will be detailed. We hope this review will provide valuable information for the development of carbohydrate-based macromolecular biomaterials and build a bridge between the carbohydrates as matter and the carbohydrates as information to promote new biomaterial design in the near future.

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Probing Sialidases or Siglecs with Sialic Acid Analogues, Clusters and Precursors

Cited by 5 publications

References 72 publications

Insights into the role of sialylation in cancer progression and metastasis

Insights into the role of sialylation in cancer progression and metastasis

The role of altered glycosylation in human nucleus pulposus cells in inflammation and degeneration

Carbohydrate-Based Macromolecular Biomaterials

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