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Host and Pathogen-Specific Drug Targets in COVID-19
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Bruce D. Uhal, David Connolly, Farzaneh Darbeheshti, Yong-Hui Zheng, Ifeanyichukwu E. Eke, Yutein Chung, Lobelia Samavati
Sialic acid decomposing drugs: One of the potentially broad-spectrum groups of antiviral drugs is decomposing sialic acid agents that target the virus entry pathway. The most common isoform of sialic acid in humans is N-acetylneuraminic acid (Neu5Ac). DAS-181, also known as Fludase, is a recombinant neuraminidase, which consists of a sialidase catalytic domain and a glycosaminoglycan-binding tag. The FDA has approved DAS181 as a therapeutic approach in hypoxic patients with lower respiratory tract parainfluenza infection.
Rat Thiostatin: Structure and Possible Function in the Acute Phase Response
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Gerhard Schreiber, Timothy J. Cole
All proteins synthesized and secreted by liver are synthesized via precursor forms (for a review, see Reference 5). After removal of the presegment, the intracellular precursors of the plasma proteins are modified further. This modification concerns the polypeptide chain or, in the case of glycoproteins, the carbohydrate moieties. In many cases, intracellular precursors of plasma proteins can be isolated (see, e.g., References 30 to 42). Also, in the case of thiostatin from Buffalo rats, it is possible to clearly separate a form of thiostatin found only in the liver from one that occurs in the plasma. Figure 5 shows the separation by anion-exchange chromatography of the two forms of thiostatin from Buffalo rat liver. The first peak corresponds to the liver form of thiostatin, the second peak to serum thiostatin. Table 2 gives a summary of the carbohydrate analysis of both liver and serum forms of Buffalo rat thiostatin. The liver thiostatin does not possess any N-acetylneuraminic acid, in contrast to the 12 mol of N-acetylneuraminic acid per 56,000 g of serum thiostatin. Also, the N-acetylglucosamine content of serum thiostatin is higher than that of liver thiostatin.
Role of Tumor Cell Membrane in Hyperthermia
Published in Leopold J. Anghileri, Jacques Robert, Hyperthermia In Cancer Treatment, 2019
One of the remarkable characteristics of glycoproteins is their viscosity and water-binding capacity. Sialic acid (N-acetylneuraminic acid) is responsible for the high viscosity and the lubricant characteristics of sialic acid-rich glycoproteins (mucins). Because of the low pK values of sialic acid, its carboxyl group is dissociated at physiologic pH. The high density of negatively charged carboxyl groups present in mucin molecules gives them an extended, rod-like, polyelectrolyte structure. The space-filling character of these molecules provokes the formation of viscoelastic gels, often with anisotropic properties. The water molecules form hydrogen bonds with disaccharide units. This type of water binding is responsible for the high water content of most tumor tissues. Glycoproteins present not only remarkable capability for water and ion binding, but also a diverse pattern of binding between macromolecules including polysaccharide-protein and polysaccharide-polysaccharide interactions.
Exploring the biomedical potential of a novel modified glass ionomer cement against the pandrug-resistant oral pathogen Candida albicans SYN-01
Published in Journal of Oral Microbiology, 2023
Nessma A. El Zawawy, Samy El-Safty, El-Refaie Kenawy, Sara Ibrahim Salem, Sameh S. Ali, Yehia A.-G. Mahmoud
Neuraminidase activity was determined using the thiobarbituric acid method [56]. Highest neuraminidase production was determined daily for 6 days titrimetrically by mucin hydrolysis for selected isolates to illustrate the optimum incubation period for enzyme production. The assay was standardized as follows: 0.5 mL of crude enzyme, 100 µL of 0.1 M sodium acetate buffer, pH 5.5, and 0.75 mg of mucin as a substrate for neuraminidase enzyme then incubated for 15 min at 37°C. Samples after incubation were treated in a water bath for 30 min at 37°C with 250 µL of the periodate reagent. With 200 µL of the sodium arsenite, the excess of periodate is then reduced. Within 1–2 min, the yellow color of the released iodine has disappeared. Then 2 mL of the reagent thiobarbituric acid (TBA) is applied, and the test sample is heated and covered for 7–5 min in a boiling water bath. In ice-water, the colored solutions are then shaken and cooled with 5 mL of butanol. By a rapid short centrifugation, the two phases were easily separated, and the absorbance was measured at 549 nm. One unit of the enzyme activity was determined as the amount of the enzyme needed to produce 1 µmoL/min of N-acetylneuraminic Acid (NANA) per min under assay condition.
Carbohydrates great and small, from dietary fiber to sialic acids: How glycans influence the gut microbiome and affect human health
Published in Gut Microbes, 2021
Joanna K Coker, Oriane Moyne, Dmitry A. Rodionov, Karsten Zengler
Thus far, we have discussed the impact of broad dietary glycan classes on the gut microbiome and host health, including how lack of fiber promotes microbial degradation of host mucus glycans. Next, we focus on the impact of dietary sialic acids, a unique and essential class of monosaccharides, on the gut microbiome and human health. Sialic acids are essential to many physiological processes, play a large role in shaping both the infant and adult microbiome, and allow exploration of how minor chemical modifications in sugar structure can shape the microbiome. Although many authors have reviewed sialic acids in the past, to our knowledge a comprehensive review focusing specifically on dietary sialic acids and the gut microbiome has not been published. In the literature, “sialic acids” is often used to refer to both the group and its most common member, N-acetylneuraminic acid. In this review, we will refer to N-acetylneuraminic acid by its abbreviation Neu5Ac and reserve the term sialic acids for the group as a whole.
Erythrocytic membrane anionic charge, sialic acid content, and their correlations with urinary glycosaminoglycans in preeclampsia and eclampsia
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2020
Papia Sen, Debdatta Ghosh, Chandan Sarkar
After overnight fasting 7 mL of blood was drawn aseptically from the antecubital vein of each participant. From this, 2 mL was used for citrated blood to estimate the EAC, 3 mL was used for heparinized blood to estimate EMSA, and the remaining 2 mL was placed in a vial with ethylenediaminetetraacetic acid (EDTA) for a complete blood hemogram. The preparation of the erythrocyte suspension from whole blood was performed according to Beutler et al. [13]. In this method, more than 99% of the white blood cells and more than 90% of the platelets were removed and approximately 97% of the erythrocytes were recovered. This suspension was used for the EAC and EMSA estimations. EAC estimation was performed according to the method of Levin using alcian blue with minor modifications [14,15]. The quantity of alcian blue bound to the erythrocytes was expressed as picomol of alcian blue/106 erythrocytes. EMSA was estimated according to the method of Spyridaki et al. [16]. N-acetylneuraminic acid was used as the standard. EMSA was expressed as nmol of membrane sialic acid/mg of erythrocytic membrane protein. Erythrocytic membrane protein was estimated according to Lowry’s method as modified by Peterson [17].