Probe sialidase substrate specificity using chemoenzymatically synthesized sialosides containing C9-modified sialic acid

2012 ◽  
Vol 48 (27) ◽  
pp. 3357 ◽  
Author(s):  
Zahra Khedri ◽  
Musleh M. Muthana ◽  
Yanhong Li ◽  
Saddam M. Muthana ◽  
Hai Yu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Substrate Specificity

scholarly journals Facile Anomer-oriented Syntheses of 4-Methylumbelliferyl Sialic Acid Glycosides

2021 ◽  
Author(s):  
Abdullah Hassan ◽  
Stefan Oscarson
Keyword(s):  
Catalytic Activity ◽  
Sialic Acid ◽  
Substrate Specificity ◽  
Enzymatic Activity ◽  
Addition Reaction ◽  
Neuraminic Acid ◽  
Acetylneuraminic Acid ◽  
Diastereoselective Addition ◽  
High Yields ◽  
Stereoselective Syntheses

<p>As part of a program to find new sialidases and determine their enzymatic specificity and catalytic activity, a library of 4-methylumbelliferyl sialic acid glycosides derivatised at the C-5 position were prepared from <i>N</i>-acetylneuraminic acid. Both α- and β-4-methylumbelliferyl sialic acid glycosides were prepared in high yields and excellent stereoselectivity. Alpha anomers were accessed via reagent control by utilising additive CH<sub>3</sub>CN and TBAI, whereas the beta anomers were synthesised through a diastereoselective addition reaction of iodine and the aglycone to the corresponding glycal followed by reduction of the resulting 3-iodo compounds. Both anomer-oriented synthetic pathways allow for gram-scale stereoselective syntheses of the desired C-5 modified neuraminic acid derivatives for use as tools to quantify the enzymatic activity and substrate specificity of known<b> </b>sialidases, and potential detection and investigation of<b> </b>novel sialidases.</p>

scholarly journals Substrate Specificity of Equine and Human Influenza A Virus Sialidase to Molecular Species of Sialic Acid

2016 ◽  
Vol 39 (10) ◽  
pp. 1728-1733 ◽  
Author(s):  
Tadanobu Takahashi ◽  
Saori Unuma ◽  
Sawako Kawagishi ◽  
Yuuki Kurebayashi ◽  
Maiko Takano ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Substrate Specificity ◽  
Influenza A Virus ◽  
Molecular Species ◽  
Influenza A ◽  
Human Influenza

scholarly journals The Sodium Sialic Acid Symporter From Staphylococcus aureus Has Altered Substrate Specificity

2018 ◽  
Vol 6 ◽  
Author(s):  
Rachel A. North ◽  
Weixiao Y. Wahlgren ◽  
Daniela M. Remus ◽  
Mariafrancesca Scalise ◽  
Sarah A. Kessans ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Sialic Acid ◽  
Substrate Specificity

scholarly journals Substrate Specificity of the Sialic Acid Biosynthetic Pathway†

Biochemistry ◽  
2001 ◽  
Vol 40 (43) ◽  
pp. 12864-12874 ◽  
Author(s):  
Christina L. Jacobs ◽  
Scarlett Goon ◽  
Kevin J. Yarema ◽  
Stephan Hinderlich ◽  
Howard C. Hang ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Substrate Specificity ◽  
Biosynthetic Pathway

scholarly journals Facile Anomer-oriented Syntheses of 4-Methylumbelliferyl Sialic Acid Glycosides

2021 ◽  
Author(s):  
Abdullah Hassan ◽  
Stefan Oscarson
Keyword(s):  
Catalytic Activity ◽  
Sialic Acid ◽  
Substrate Specificity ◽  
Enzymatic Activity ◽  
Addition Reaction ◽  
Neuraminic Acid ◽  
Acetylneuraminic Acid ◽  
Diastereoselective Addition ◽  
High Yields ◽  
Stereoselective Syntheses

<p>As part of a program to find new sialidases and determine their enzymatic specificity and catalytic activity, a library of 4-methylumbelliferyl sialic acid glycosides derivatised at the C-5 position were prepared from <i>N</i>-acetylneuraminic acid. Both α- and β-4-methylumbelliferyl sialic acid glycosides were prepared in high yields and excellent stereoselectivity. Alpha anomers were accessed via reagent control by utilising additive CH<sub>3</sub>CN and TBAI, whereas the beta anomers were synthesised through a diastereoselective addition reaction of iodine and the aglycone to the corresponding glycal followed by reduction of the resulting 3-iodo compounds. Both anomer-oriented synthetic pathways allow for gram-scale stereoselective syntheses of the desired C-5 modified neuraminic acid derivatives for use as tools to quantify the enzymatic activity and substrate specificity of known<b> </b>sialidases, and potential detection and investigation of<b> </b>novel sialidases.</p>

scholarly journals Structural Basis for the Divergence of Substrate Specificity and Biological Function within HAD Phosphatases in Lipopolysaccharide and Sialic Acid Biosynthesis

Biochemistry ◽  
2013 ◽  
Vol 52 (32) ◽  
pp. 5372-5386 ◽  
Author(s):  
Kelly D. Daughtry ◽  
Hua Huang ◽  
Vladimir Malashkevich ◽  
Yury Patskovsky ◽  
Weifeng Liu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Substrate Specificity ◽  
Biological Function ◽  
Structural Basis ◽  
Acid Biosynthesis

scholarly journals Chemoenzymatic synthesis of para-nitrophenol (pNP)-tagged α2–8-sialosides and high-throughput substrate specificity studies of α2–8-sialidases

2017 ◽  
Vol 15 (1) ◽  
pp. 160-167 ◽  
Author(s):  
Nova Tasnima ◽  
Hai Yu ◽  
Yanhong Li ◽  
Abhishek Santra ◽  
Xi Chen
Keyword(s):  
Sialic Acid ◽  
Substrate Specificity ◽  
High Throughput ◽  
Chemoenzymatic Synthesis

para-Nitrophenyl α2–8-sialosides containing different sialic acid forms were chemoenzymatically synthesized and used as effective probes for high-throughput substrate specificity studies of the α2–8-sialidase activities of human and bacterial sialidases.

scholarly journals Amino Acid Residues Contributing to the Substrate Specificity of the Influenza A Virus Neuraminidase

1999 ◽  
Vol 73 (8) ◽  
pp. 6743-6751 ◽  
Author(s):  
Darwyn Kobasa ◽  
Shantha Kodihalli ◽  
Ming Luo ◽  
Maria R. Castrucci ◽  
Isabella Donatelli ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Amino Acid ◽  
Substrate Specificity ◽  
Viral Replication ◽  
Active Site ◽  
Influenza A ◽  
Sialic Acids ◽  
Influenza A Viruses ◽  
Human Viruses

ABSTRACT Influenza A viruses possess two glycoprotein spikes on the virion surface: hemagglutinin (HA), which binds to oligosaccharides containing terminal sialic acid, and neuraminidase (NA), which removes terminal sialic acid from oligosaccharides. Hence, the interplay between these receptor-binding and receptor-destroying functions assumes major importance in viral replication. In contrast to the well-characterized role of HA in host range restriction of influenza viruses, there is only limited information on the role of NA substrate specificity in viral replication among different animal species. We therefore investigated the substrate specificities of NA for linkages betweenN-acetyl sialic acid and galactose (NeuAcα2-3Gal and NeuAcα2-6Gal) and for different molecular species of sialic acids (N-acetyl and N-glycolyl sialic acids) in influenza A viruses isolated from human, avian, and pig hosts. Substrate specificity assays showed that all viruses had similar specificities for NeuAcα2-3Gal, while the activities for NeuAcα2-6Gal ranged from marginal, as represented by avian and early N2 human viruses, to high (although only one-third the activity for NeuAcα2-3Gal), as represented by swine and more recent N2 human viruses. Using site-specific mutagenesis, we identified in the earliest human virus with a detectable increase in NeuAcα2-6Gal specificity a change at position 275 (from isoleucine to valine) that enhanced the specificity for this substrate. Valine at position 275 was maintained in all later human viruses as well as swine viruses. A similar examination of N-glycolylneuraminic acid (NeuGc) specificity showed that avian viruses and most human viruses had low to moderate activity for this substrate, with the exception of most human viruses isolated between 1967 and 1969, whose NeuGc specificity was as high as that of swine viruses. The amino acid at position 431 was found to determine the level of NeuGc specificity of NA: lysine conferred high NeuGc specificity, while proline, glutamine, and glutamic acid were associated with lower NeuGc specificity. Both residues 275 and 431 lie close to the enzymatic active site but are not directly involved in the reaction mechanism. This finding suggests that the adaptation of NA to different substrates occurs by a mechanism of amino acid substitutions that subtly alter the conformation of NA in and around the active site to facilitate the binding of different species of sialic acid.

Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

2003 ◽  
Vol 70 ◽  
pp. 39-52 ◽  
Author(s):  
Roy A. Black ◽  
John R. Doedens ◽  
Rajeev Mahimkar ◽  
Richard Johnson ◽  
Lin Guo ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Recent Work ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transforming Growth Factor ◽  
Intrinsic Activity ◽  
Converting Enzyme ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

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