Chemo-enzymatic synthesis of C-9 acetylated sialosides

Background: Specificity and enzymology of glycan sialylation is poorly understood, despite its importance in biological recognition. Results: ST6GAL1 structure was determined, and substrate binding was modeled to probe active site specificity. Conclusion:The structure provides insights into the enzymatic basis of glycan sialylation. Significance: Knowledge of the enzyme structure can lead to broader understanding of enzymatic sialylation and selective inhibitor design.

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“…5). This orientation is consistent with a tolerance of the enzyme toward sugar donor modifications at O9 and the N-acetyl groups (81,82).…”

Section: Modeling Molecular Dynamics Simulations Of Substrate Interasupporting

confidence: 61%

Enzymatic Basis for N-Glycan Sialylation

Forouhar

Thieker

et al. 2013

Journal of Biological Chemistry

120

130

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“…In support of this, CMP-Neu5,9Ac 2 was detected in bovine submandibular glands 54 and biochemical data obtained with human colon mucosa showed a Golgi-associated SOAT activity that utilized CMP-Neu5Ac as acceptor and a sialyltransferase activity that transferred 9- O -acetylated Sia from CMP-Neu5,9Ac 2 to endogenous and exogenous acceptors 33 , 55 . Moreover, the use of CMP-Neu5,9Ac 2 has been shown for several sialyltransferases and is exploited for chemo-enzymatic synthesis of 9- O -acetylated sialosides 56 . In vivo , the efficient and selective usage of CMP-Neu5,9Ac 2 may rely on a physical interaction between CASD1 and specific sialyltransferases.…”

Section: Discussionmentioning

confidence: 99%

9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate

et al. 2015

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Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host–pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1—a previously identified human candidate gene—is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans.

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“…Prepared by employing a glycosyl donor having a participating (S)-(phenylthiomethyl)benzyl moiety at C-6 C-9 Acetylated sialosides TOF (DHB) Chemo-enzymatic synthesis (Rauvolfova, et al, 2008) Aminoethyl…”

Section: Maldi-ftms (No Matrix)mentioning

confidence: 99%

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2007–2008

Harvey

2011

Mass Spectrometry Reviews

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This review is the fifth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2008. The first section of the review covers fundamental studies, fragmentation of carbohydrate ions, use of derivatives and new software developments for analysis of carbohydrate spectra. Among newer areas of method development are glycan arrays, MALDI imaging and the use of ion mobility spectrometry. The second section of the review discusses applications of MALDI MS to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N- and O-linked glycans from glycoproteins, biopharmaceuticals, glycated proteins, glycolipids, glycosides and various other natural products. There is a short section on the use of MALDI mass spectrometry for the study of enzymes involved in glycan processing and a section on the use of MALDI MS to monitor products of the chemical synthesis of carbohydrates with emphasis on carbohydrate-protein complexes and glycodendrimers. Corresponding analyses by electrospray ionization now appear to outnumber those performed by MALDI and the amount of literature makes a comprehensive review on this technique impractical. However, most of the work relating to sample preparation and glycan synthesis is equally relevant to electrospray and, consequently, those proposing analyses by electrospray should also find material in this review of interest.

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Chemo-enzymatic synthesis of C-9 acetylated sialosides

Cited by 16 publications

References 38 publications

Enzymatic Basis for N-Glycan Sialylation

Enzymatic Basis for N-Glycan Sialylation

9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2007–2008

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