Reversible O-Acetyl Migration within the Sialic Acid Side Chain and Its Influence on Protein Recognition

2021 ◽  
Author(s):  
Yang Ji ◽  
Aniruddha Sasmal ◽  
Wanqing Li ◽  
Lisa Oh ◽  
Saurabh Srivastava ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Side Chain ◽  
Protein Recognition ◽  
Acetyl Migration

scholarly journals Biochemical engineering of theN-acyl side chain of sialic acid leads to increased calcium influx from intracellular compartments and promotes differentiation of HL60 cells

FEBS Letters ◽  
2004 ◽  
Vol 571 (1-3) ◽  
pp. 99-102 ◽  
Author(s):  
Rüdiger Horstkorte ◽  
Kirstin Rau ◽  
Stephan Laabs ◽  
Kerstin Danker ◽  
Werner Reutter
Keyword(s):  
Sialic Acid ◽  
Calcium Influx ◽  
Side Chain ◽  
Biochemical Engineering ◽  
Hl60 Cells ◽  
Acyl Side Chain ◽  
Intracellular Compartments

Glycoengineering the N-acyl side chain of sialic acid of human erythropoietin affects its resistance to sialidase

2012 ◽  
Vol 393 (8) ◽  
pp. 777-783 ◽  
Author(s):  
Anselm Werner ◽  
Rüdiger Horstkorte ◽  
Dagobert Glanz ◽  
Karina Biskup ◽  
Véronique Blanchard ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Culture Medium ◽  
Sialic Acids ◽  
Side Chain ◽  
Cell Culture Medium ◽  
Terminal Position ◽  
Human Erythropoietin ◽  
Recombinant Glycoproteins ◽  
Complex Glycans ◽  
Over Time

Abstract During the last years, the use of therapeutic glycoproteins has increased strikingly. Glycosylation of recombinant glycoproteins is of major importance in biotechnology, as the glycan composition of recombinant glycoproteins impacts their pharmacological properties. The terminal position of N-linked complex glycans in mammals is typically occupied by sialic acid. The presence of sialic acid is crucial for functionality and affects the half-life of glycoproteins. However, glycoproteins in the bloodstream become desialylated over time and are recognized by the asialoglycoprotein receptors via the exposed galactose and targeted for degradation. Non-natural sialic acid precursors can be used to engineer the glycosylation side chains by biochemically introducing new non-natural terminal sialic acids. Previously, we demonstrated that the physiological precursor of sialic acid (i.e., N-acetylmannosamine) can be substituted by the non-natural precursors N-propanoylmannosamine (ManNProp) or N-pentanoylmannosamine (ManNPent) by their simple application to the cell culture medium. Here, we analyzed the glycosylation of erythropoietin (EPO). By feeding cells with ManNProp or ManNPent, we were able to incorporate N-propanoyl or N-pentanoyl sialic acid in significant amounts into EPO. Using a degradation assay with sialidase, we observed a higher resistance of EPO to sialidase after incorporation of N-propanoyl or N-pentanoyl sialic acid.

scholarly journals Glycosphingolipid Binding Specificities of Rotavirus: Identification of a Sialic Acid-Binding Epitope

2001 ◽  
Vol 75 (5) ◽  
pp. 2276-2287 ◽  
Author(s):  
Cécile Delorme ◽  
Harald Brüssow ◽  
Josette Sidoti ◽  
Niamh Roche ◽  
Karl-Anders Karlsson ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Binding Assay ◽  
Side Chain ◽  
Terminal Sequence ◽  
Thin Layer Chromatogram ◽  
Structural Element ◽  
Neuraminidase Treatment ◽  
Viral Particles ◽  
Binding Epitope ◽  
Sialic Acid Binding

ABSTRACT The glycosphingolipid binding specificities of neuraminidase-sensitive (simian SA11 and bovine NCDV) and neuraminidase-insensitive (bovine UK) rotavirus strains were investigated using the thin-layer chromatogram binding assay. Both triple-layered and double-layered viral particles of SA11, NCDV, and UK bound to nonacid glycosphingolipids, including gangliotetraosylceramide (GA1; also called asialo-GM1) and gangliotriaosylceramide (GA2; also called asialo-GM2). Binding to gangliosides was observed with triple-layered particles but not with double-layered particles. The neuraminidase-sensitive and neuraminidase-insensitive rotavirus strains showed distinct ganglioside binding specificities. All three strains bound to sialylneolactotetraosylceramide and GM2 and GD1a gangliosides. However, NeuAc-GM3 and the GM1 ganglioside were recognized by rotavirus strain UK but not by strains SA11 and NCDV. Conversely, NeuGc-GM3 was bound by rotaviruses SA11 and NCDV but not by rotavirus UK. Thus, neuraminidase-sensitive strains bind to external sialic acid residues in gangliosides, while neuraminidase-insensitive strains recognize gangliosides with internal sialic acids, which are resistant to neuraminidase treatment. By testing a panel of gangliosides with triple-layered particles of SA11 and NCDV, the terminal sequence sialyl-galactose (NeuGc/NeuAcα3-Galβ) was identified as the minimal structural element required for the binding of these strains. The binding of triple-layered particles of SA11 and NCDV to NeuGc-GM3, but not to NeuAc-GM3, suggested that the sequence NeuGcα3Galβ is preferred to NeuAcα3Galβ. Further dissection of this binding epitope showed that the carboxyl group and glycerol side chain of sialic acid played an important role in the binding of such triple-layered particles.

scholarly journals Cross-comparison of Protein Recognition of Sialic Acid Diversity on Two Novel Sialoglycan Microarrays

2012 ◽  
Vol 287 (27) ◽  
pp. 22593-22608 ◽  
Author(s):  
Vered Padler-Karavani ◽  
Xuezheng Song ◽  
Hai Yu ◽  
Nancy Hurtado-Ziola ◽  
Shengshu Huang ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Protein Recognition

scholarly journals Elucidation of the topological parameters of N-acetylneuraminic acid and some analogues involved in their interaction with the N-acetylneuraminate lyase from Clostridium perfringens

1992 ◽  
Vol 282 (2) ◽  
pp. 511-516 ◽  
Author(s):  
E Zbiral ◽  
R G Kleineidam ◽  
E Schreiner ◽  
M Hartmann ◽  
R Christian ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Oxygen Atom ◽  
Clostridium Perfringens ◽  
Pyruvic Acid ◽  
Sialic Acids ◽  
Side Chain ◽  
Equatorial Zone ◽  
Enzyme Action ◽  
Acetylneuraminic Acid ◽  
Topological Parameters

A series of neuraminic acid derivatives modified in the side chain or at C-3, C-4 or C-5 were tested as substrates of inhibitors of N-acetylneuraminate lyase (EC 4.1.3.3) from Clostridium perfringens. The results, together with Km and Ki values reported previously, indicate that the region most important for the binding of sialic acids is an equatorial zone reaching from C-8 via the ring oxygen atom to C-4 of the sugar molecule, whereas the substituents at C-9 and C-5 may be varied to a higher extent without significantly disturbing enzyme action. It is shown that stereo-electronic factors are responsible for the immediate heterolytic fragmentation of the cyclic sialic acid into pyruvic acid and 2-acetamidomannose or a related C-6 sugar.

scholarly journals α2,3 linkage of sialic acid to a GPI anchor and an unpredicted GPI attachment site in human prion protein

2020 ◽  
Vol 295 (22) ◽  
pp. 7789-7798 ◽  
Author(s):  
Atsushi Kobayashi ◽  
Tetsuya Hirata ◽  
Takashi Nishikaze ◽  
Akinori Ninomiya ◽  
Yuta Maki ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Prion Protein ◽  
Prion Diseases ◽  
Attachment Site ◽  
Cellular Prion Protein ◽  
Side Chain ◽  
Glycan Structure ◽  
Gpi Anchor ◽  
Acetylneuraminic Acid ◽  
Sialic Acid Linkage

Prion diseases are transmissible, lethal neurodegenerative disorders caused by accumulation of the aggregated scrapie form of the prion protein (PrPSc) after conversion of the cellular prion protein (PrPC). The glycosylphosphatidylinositol (GPI) anchor of PrPC is involved in prion disease pathogenesis, and especially sialic acid in a GPI side chain reportedly affects PrPC conversion. Thus, it is important to define the location and structure of the GPI anchor in human PrPC. Moreover, the sialic acid linkage type in the GPI side chain has not been determined for any GPI-anchored protein. Here we report GPI glycan structures of human PrPC isolated from human brains and from brains of a knock-in mouse model in which the mouse prion protein (Prnp) gene was replaced with the human PRNP gene. LC–electrospray ionization–MS analysis of human PrPC from both biological sources indicated that Gly229 is the ω site in PrPC to which GPI is attached. Gly229 in human PrPC does not correspond to Ser231, the previously reported ω site of Syrian hamster PrPC. We found that ∼41% and 28% of GPI anchors in human PrPCs from human and knock-in mouse brains, respectively, have N-acetylneuraminic acid in the side chain. Using a sialic acid linkage-specific alkylamidation method to discriminate α2,3 linkage from α2,6 linkage, we found that N-acetylneuraminic acid in PrPC's GPI side chain is linked to galactose through an α2,3 linkage. In summary, we report the GPI glycan structure of human PrPC, including the ω-site amino acid for GPI attachment and the sialic acid linkage type.

Structure determination ofStreptococcus suisserotype 14 capsular polysaccharide

2013 ◽  
Vol 91 (2) ◽  
pp. 49-58 ◽  
Author(s):  
Marie-Rose Van Calsteren ◽  
Fleur Gagnon ◽  
Cynthia Calzas ◽  
Guillaume Goyette-Desjardins ◽  
Masatoshi Okura ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Capsular Polysaccharide ◽  
Group B Streptococcus ◽  
Periodate Oxidation ◽  
Side Chain ◽  
Chemically Modified ◽  
Type Ia ◽  
Group B ◽  
Suis Serotype ◽  
Mild Acid

The capsular polysaccharide (CPS) of Streptococcus suis serotype 14 was purified, chemically modified, and characterized. Sugar and absolute configuration analyses gave the following CPS composition: d-Gal, 3; d-Glc, 1; d-GlcNAc, 1; d-Neu5Ac, 1. The Sambucus nigra lectin, which recognizes the Neu5Ac(α2–6)Gal/GalNAc sequence, showed binding to the native CPS. Sialic acid was found to be terminal, and the CPS was quantitatively desialylated by mild acid hydrolysis. It was also submitted to periodate oxidation followed by borohydride reduction and Smith degradation. Sugar and methylation analyses,1H and13C nuclear magnetic resonance, and mass spectrometry of the native CPS or of its specifically modified products allowed to determine the repeating unit sequence: [6)[Neu5Ac(α2–6)Gal(β1–4)GlcNAc(β1–3)]Gal(β1–3)Gal(β1–4)Glc(β1–]n. S. suis serotype 14 CPS has an identical sialic acid-containing side chain as serotype 2 CPS, but differs by the absence of rhamnose in its composition. The same side chain is also present in group B Streptococcus type Ia CPS, except that in the latter sialic acid is 2,3- rather than 2,6-linked to the following galactose. A correlation between the S. suis CPS sequence and genes of the serotype 14 cps locus encoding putative glycosyltransferases and polymerase responsible for the biosynthesis of the repeating unit is proposed.

Removal of O-acetylated sialic acids from rat colonic epithelial glycoproteins by cell-free extracts of rat faeces

1983 ◽  
Vol 61 (8) ◽  
pp. 868-874 ◽  
Author(s):  
H. Poon ◽  
P. E. Reid ◽  
C. W. Ramey ◽  
W. L. Dunn ◽  
M. G. Clay
Keyword(s):  
Sialic Acid ◽  
Acid Content ◽  
Minimal Medium ◽  
Wistar Rat ◽  
Sialic Acids ◽  
Side Chain ◽  
Sialic Acid Content ◽  
Vibrio Cholera ◽  
Sterile Cell

Sterile, cell-free, extracts of freshly defaecated Wistar rat faeces in a pH 7.0 "minimal medium" contain neuraminidase(s), capable of removing sialic acids both with and without side-chain substituents from bovine submandibular mucin and rat colonic epithelial glycoproteins, and an esterase which removes O-acetyl substituents from the side chain of sialic acid residues. Studies of the removal of sialic acids from bovine submandibular mucin and rat colonic epithelial glycoproteins indicated that (i) the faecal enzymes removed a greater proportion of the sialic acid of both the de-O-acetylated and native glycoproteins than was removed with Vibrio cholera neuraminidase, (ii) sialic acids were removed more rapidly from de-O-acetylated glycoproteins, and (iii) the resistance to removal of sialic acids was apparently dependent at least in part upon the O-acetyl sialic acid content of the substrate.

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