A Modular Chemoenzymatic Synthesis of Disialosyl Globopentaosylceramide (DSGb5Cer) Glycan

Wu, Dung-Yeh; Adak, Asok; Kuo, Yan-Ting; Shen, Yu‐Ju; Li, Pei-Jhen; Hwu, Jih Ru; Lin, Chun Cheng

doi:10.1021/acs.joc.0c01091

Cited by 5 publications

(9 citation statements)

References 46 publications

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“…Disialosyl globopentaosylceramide (DSGb5) is a dominant ganglioside isolated from RCC tissues [ 70 ] which binds to sialic acid-binding Ig-like lectin-7 (Siglec-7) expressed on natural killer (NK) cells, thereby inhibiting NK-cell cytotoxicity [ 71 ]. Higher DSGb5 expression exhibits greater migration potential in ACHN RCC cells and is correlated with metastasis in RCC patients [ 71 , 72 ].…”

Section: Glycosphingolipids In Renal Cancermentioning

confidence: 99%

Lipids as Targets for Renal Cell Carcinoma Therapy

Tanturovska

Manaila

Fabbro³

et al. 2023

IJMS

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Kidney cancer is among the top ten most common cancers to date. Within the kidney, renal cell carcinoma (RCC) is the most common solid lesion occurring. While various risk factors are suspected, including unhealthy lifestyle, age, and ethnicity, genetic mutations seem to be a key risk factor. In particular, mutations in the von Hippel–Lindau gene (Vhl) have attracted a lot of interest since this gene regulates the hypoxia inducible transcription factors HIF-1α and HIF-2α, which in turn drive the transcription of many genes that are important for renal cancer growth and progression, including genes involved in lipid metabolism and signaling. Recent data suggest that HIF-1/2 are themselves regulated by bioactive lipids which make the connection between lipids and renal cancer obvious. This review will summarize the effects and contributions of the different classes of bioactive lipids, including sphingolipids, glycosphingolipids, eicosanoids, free fatty acids, cannabinoids, and cholesterol to renal carcinoma progression. Novel pharmacological strategies interfering with lipid signaling to treat renal cancer will be highlighted.

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Section: Glycosphingolipids In Renal Cancermentioning

confidence: 99%

Lipids as Targets for Renal Cell Carcinoma Therapy

Tanturovska

Manaila

Fabbro³

et al. 2023

IJMS

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“…These enzymes specifically catalyze α2,3 sialylation to terminal Gal and α2,6 sialylation to GalNAc, respectively. Although the chemical synthesis of di-sialylated glycolipid was also reported, chemical synthesis requires several deprotection steps after each sialylation, which is time-consuming and lowers the yield [ 125 ]. It was shown that sialylated multi-antennary N -glycans can be synthesized by human ST6Gal1 and ST3Gal4, each of which recognizes LacNAc as acceptor [ 126 ].…”

Section: Manipulating Sialyltransferases At a Molecular Levelmentioning

confidence: 99%

Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems

2021

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Glycans have been shown to play a key role in many biological processes, such as signal transduction, immunogenicity, and disease progression. Among the various glycosylation modifications found on cell surfaces and in biomolecules, sialylation is especially important, because sialic acids are typically found at the terminus of glycans and have unique negatively charged moieties associated with cellular and molecular interactions. Sialic acids are also crucial for glycosylated biopharmaceutics, where they promote stability and activity. In this regard, heterogenous sialylation may produce variability in efficacy and limit therapeutic applications. Homogenous sialylation may be achieved through cellular and molecular engineering, both of which have gained traction in recent years. In this paper, we describe the engineering of intracellular glycosylation pathways through targeted disruption and the introduction of carbohydrate active enzyme genes. The focus of this review is on sialic acid-related genes and efforts to achieve homogenous, humanlike sialylation in model hosts. We also discuss the molecular engineering of sialyltransferases and their application in chemoenzymatic sialylation and sialic acid visualization on cell surfaces. The integration of these complementary engineering strategies will be useful for glycoscience to explore the biological significance of sialic acids on cell surfaces as well as the future development of advanced biopharmaceuticals.

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“…[23] Several research groups have proposed both enzymatic and chemoenzymatic methods of preparing globo-series glycans such as SSEA-3 (Gb5), SSEA-4 (MSGb5), Globo H, and DSGb5. [24][25][26][27] However, only a few total chemical syntheses of globo-series GSL are available, and the requirement for extensive selective protection/deprotection steps and stereoselective conversion of glycosyl donors to GSLs result in a large number of steps and low overall yield. [28,29] Alternatively, the coupling of chemoenzymatically generated α-glycosyl fluorides and Sph components have been reported for the synthesis of GSLs in an engineered glycosynthase-catalyzed reaction.…”

Section: Introductionmentioning

confidence: 99%

“…Several research groups have proposed both enzymatic and chemoenzymatic methods of preparing globo‐series glycans such as SSEA‐3 (Gb5), SSEA‐4 (MSGb5), Globo H, and DSGb5 [24–27] . However, only a few total chemical syntheses of globo‐series GSL are available, and the requirement for extensive selective protection/deprotection steps and stereoselective conversion of glycosyl donors to GSLs result in a large number of steps and low overall yield [28,29] .…”

Section: Introductionmentioning

confidence: 99%

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Chemoenzymatic Synthesis of Globo‐series Glycosphingolipids and Evaluation of Their Immunosuppressive Activities

Chiang

Adak

Liang

et al. 2022

Chemistry An Asian Journal

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Glycosphingolipids (GSLs) play essential roles in many important biological processes, making them attractive synthetic targets. In this paper, a viable chemoenzymatic method is described for the synthesis of globo-series GSLs, namely, Gb4, Gb5, SSEA-4, and Globo H. The strategy uses a chemically synthesized lactoside acceptor equipped with a partial ceramide structure that is uniquely extended by glycosyltransferases in a highly efficient one-pot multiple enzyme (OPME) procedure. A direct and quantitative conversion of Gb4 sphingosine to Globo H sphingosine is achieved by performing two-sequential OPME glycosylations. A reduction and N-acylation protocol allows facile incorporation of various fatty acids into the lipid portions of the GSLs. The chemically well-defined lipid-modified Globo H-GSLs displayed some differences in their immunosuppressive activities, which may benefit the structural modifications of Globo H ceramides in finding new types of immunosuppressive agents. The strategy outlined in this work should be applicable to the rapid access to other complex GSLs.

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A Modular Chemoenzymatic Synthesis of Disialosyl Globopentaosylceramide (DSGb5Cer) Glycan

Cited by 5 publications

References 46 publications

Lipids as Targets for Renal Cell Carcinoma Therapy

Lipids as Targets for Renal Cell Carcinoma Therapy

Cellular and Molecular Engineering of Glycan Sialylation in Heterologous Systems

Chemoenzymatic Synthesis of Globo‐series Glycosphingolipids and Evaluation of Their Immunosuppressive Activities

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