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Sialic Acid

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https://www.readbyqxmd.com/read/29684709/the-role-of-natural-selection-in-shaping-genetic-variation-in-a-promising-chagas-disease-drug-target-trypanosoma-cruzi-trans-sialidase
#1
Joseph P Gallant, Raquel Asunción Lima-Cordón, Silvia Justi, Maria Carlota Monroy, Toni Viola, Lori Stevens
Rational drug design creates innovative therapeutics based on knowledge of the biological target to provide more effective and responsible therapeutics. Chagas disease, endemic throughout Latin America, is caused by Trypanosoma cruzi, a protozoan parasite. Current therapeutics are problematic with widespread calls for new approaches. Researchers are using rational drug design for Chagas disease and one target receiving considerable attention is the T. cruzi trans-sialidase protein (TcTS). In T. cruzi, trans-sialidase catalyzes the transfer of sialic acid from a mammalian host to coat the parasite surface membrane and avoid immuno-detection...
April 20, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29680984/serum-sialylation-changes-in-cancer
#2
REVIEW
Zejian Zhang, Manfred Wuhrer, Stephanie Holst
Cancer is a major cause of death in both developing and developed countries. Early detection and efficient therapy can greatly enhance survival. Aberrant glycosylation has been recognized to be one of the hallmarks of cancer as glycans participate in many cancer-associated events. Cancer-associated glycosylation changes often involve sialic acids which play important roles in cell-cell interaction, recognition and immunological response. This review aims at giving a comprehensive overview of the literature on changes of sialylation in serum of cancer patients...
April 21, 2018: Glycoconjugate Journal
https://www.readbyqxmd.com/read/29678922/enzymatic-synthesis-of-6-sialyllactose-a-dominant-sialylated-human-milk-oligosaccharide-by-a-novel-exo-%C3%AE-sialidase-from-bacteroides-fragilis-nctc9343
#3
Longcheng Guo, Xiaodi Chen, Li Xu, Min Xiao, Lili Lu
Gut bacteria provide a rich source of glycosidases that can recognize and/or hydrolyze glycans for nutritions. Interestingly, some glycosidases are also found to catalyze transglycosylation reactions in vitro and thus can be used for oligosaccharide synthesis. In this work, six putative and one known exo -α-sialidase genes, including three from Bacteroides fragilis NCTC9343, three from Clostridium perfringens ATCC13124, and one known from Bifidobacterium bifidum JCM1254, were subjected to gene cloning and heterogeneous expression in Escherichia coli The recombinant enzymes were purified, characterized for substrate specificity, and screened for transglycosylation activity...
April 20, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29678767/targeted-inhibition-of-tumor-survival-metastasis-and-angiogenesis-by-acacia-ferruginea-mediated-regulation-of-vegf-inflammatory-mediators-cytokine-profile-and-inhibition-of-transcription-factor-activation
#4
Kunnathur Murugesan Sakthivel, Chandrasekaran Guruvayoorappan
Acacia ferruginea extract (AFE) was studied for anti-metastasis/-angiogenesis activity against B16F-10 melanoma cells in C57BL/6 mice. In vitro cytotoxicity of AFE was first screened using MTT assay and it was shown to inhibit B16F-10 cells with IC50 value of 52.94 μg/ml. Anti-metastatic activity of AFE in vivo revealed administration of AFE (10 mg/kg.b.wt) in three different regimens has shown reduced metastatic colony formation in lungs and prolonged survival in metastatic tumor-bearing hosts. Biochemical analysis shown that treatment with AFE significantly reduced the lung collagen hydroxyproline, hexosamine, uronic acid, sialic acid and gamma-glutamyl transpeptidase content...
April 17, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29674446/polysialic-acid-is-a-cellular-receptor-for-human-adenovirus-52
#5
Annasara Lenman, A Manuel Liaci, Yan Liu, Lars Frängsmyr, Martin Frank, Bärbel S Blaum, Wengang Chai, Iva I Podgorski, Balázs Harrach, Mária Benkő, Ten Feizi, Thilo Stehle, Niklas Arnberg
Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29674057/high-resolution-glycoform-profiling-of-intact-therapeutic-proteins-by-hydrophilic-interaction-chromatography-mass-spectrometry
#6
Elena Domínguez-Vega, Sara Tengattini, Claudia Peintner, Jordy van Angeren, Caterina Temporini, Rob Haselberg, Gabriella Massolini, Govert W Somsen
Glycosylation is considered a critical quality attribute of therapeutic proteins. Protein heterogeneity introduced by glycosylation includes differences in the nature, number and position of the glycans. Whereas analysis of released glycans and glycopeptides provides information about the composition and/or position of the glycan, intact glycoprotein analysis allows assignment of individual proteoforms and co-occurring modifications. Yet, resolving protein glycoforms at the intact level is challenging. We have explored the capacity of hydrophilic liquid chromatography-mass spectrometry (HILIC-MS) for assessing glycosylation patterns of intact pharmaceutical proteins by analyzing the complex glycoproteins interferon-beta-1a (rhIFN-β - 1a) and recombinant human erythropoietin (rhEPO)...
July 1, 2018: Talanta
https://www.readbyqxmd.com/read/29672630/nonclinical-comparability-studies-of-recombinant-human-arylsulfatase-a-addressing-manufacturing-process-changes
#7
Teresa Wright, Aiqun Li, Jason Lotterhand, Anne-Renee Graham, Yan Huang, Nancy Avila, Jing Pan
Recombinant human arylsulfatase A (rhASA) is in clinical development for the treatment of patients with metachromatic leukodystrophy (MLD). Manufacturing process changes were introduced to improve robustness and efficiency, resulting in higher levels of mannose-6-phosphate and sialic acid in post-change (process B) compared with pre-change (process A) rhASA. A nonclinical comparability program was conducted to compare process A and process B rhASA. All doses were administered intrathecally. Pharmacodynamic comparability was evaluated in immunotolerant MLD mice, using immunohistochemical staining of lysosomal-associated membrane protein-1 (LAMP-1)...
2018: PloS One
https://www.readbyqxmd.com/read/29671762/increased-level-of-%C3%AE-2-6-sialylated-glycans-on-hacat-cells-induced-by-titanium-dioxide-nanoparticles-under-uv-radiation
#8
Yuanyuan Ren, Xin Liu, Runqing Geng, Qunwei Lu, Rong Rao, Xi Tan, Xiangliang Yang, Wei Liu
As one of the most widely used nanomaterials, the safety of nano-TiO₂ for human beings has raised concern in recent years. Sialylation is an important glycosylation modification that plays a critical role in signal transduction, apoptosis, and tumor metastasis. The aim of this work was to investigate the cytotoxicity and phototoxicity of nano-TiO₂ with different crystalline phases for human skin keratinocytes (HaCaT cells) under ultraviolet (UV) irradiation and detect sialic acid alterations. The results showed that the mixture of crystalline P25 had the highest cytotoxicity and phototoxicity, followed by pure anatase A25, whereas pure rutile R25 had the lowest cytotoxicity and phototoxicity...
April 19, 2018: Nanomaterials
https://www.readbyqxmd.com/read/29666608/capsular-sialyltransferase-specificity-mediates-different-phenotypes-in-streptococcus-suis-and-group-b-streptococcus
#9
David Roy, Daisuke Takamatsu, Masatoshi Okura, Guillaume Goyette-Desjardins, Marie-Rose Van Calsteren, Audrey Dumesnil, Marcelo Gottschalk, Mariela Segura
The capsular polysaccharide (CPS) represents a key virulence factor for most encapsulated streptococci. Streptococcus suis and Group B Streptococcus (GBS) are both well-encapsulated pathogens of clinical importance in veterinary and/or human medicine and responsible for invasive systemic diseases. S. suis and GBS are the only Gram-positive bacteria which express a sialylated CPS at their surface. An important difference between these two sialylated CPSs is the linkage between the side-chain terminal galactose and sialic acid, being α-2,6 for S...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29663501/the-effect-of-plant-lectins-on-the-survival-and-malignant-behaviors-of-thyroid-cancer-cells
#10
Engin Kaptan, Serap Sancar-Bas, Aylin Sancakli, Suna Bektas, Sehnaz Bolkent
Altered or aberrant glycosylation is a common phenomenon in cancer cells and it originates from changes in the expression of the enzymes, glycosyltransferase, and glycosidase which up-regulate in response to some oncogenes in the glycan synthesis pathway. In this present study, it has been aimed to determine the alteration of sialic acid and fucose expressions in the cell surface of human thyroid carcinoma cells and investigate the changes in tumorigenic and malignant characters after treating them with specific plant lectins...
April 16, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29661931/the-role-of-neuraminidase-producing-bacteria-in-exposing-cryptic-carbohydrate-receptors-for-streptococcus-gordonii-adherence
#11
Alex Wong, Margaret A Grau, Anirudh K Singh, Shireen A Woodiga, Samantha J King
Streptococcus gordonii is an early colonizer of the oral cavity. Although a variety of S. gordonii adherence mechanisms have been described, current dogma is that the major receptor for S. gordonii is sialic acid. However, as many bacterial species in the oral cavity produce neuraminidase that can cleave terminal sialic acid, it is unclear whether S. gordonii relies on sialic acid for adherence to oral surfaces or if this species has developed alternative binding strategies. Previous studies have examined adherence to immobilized glycoconjugates and identified binding to additional glycans; but no prior studies have defined the contribution of these different glycan structures in adherence to oral epithelial cells...
April 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29658283/-oligo-and-polysacharides-proteoglycans
#12
Lajos Jakab
After clearing up the confusion in the previously used nomenclature, the paper discusses the family of small-leucin-rich glycoproteins. After mentioning the family and its role in the organisation of the ground substance and in the regulation of inflammation, one unique molecule of proteoglycans is presented. This molecule is the inter-α-trypsin inhibitor. It has turned out that this peculiar molecule originally contains glycosaminoglycan beside the neutral carbohydrates. After summarizing the numerous connections of the proteoglycan molecule, the "self-sacrificing" nature of the molecule is presented...
April 2018: Orvosi Hetilap
https://www.readbyqxmd.com/read/29651731/identification-of-sialic-acid-linkages-on-intact-glycopeptides-via-differential-chemical-modification-using-intactgig-hilic
#13
Shuang Yang, Wells W Wu, Rong-Fong Shen, Marshall Bern, John Cipollo
Mass spectrometric analysis of intact glycopeptides can reveal detailed information about glycosite, glycan structural features, and their heterogeneity. Sialyl glycopeptides can be positively, negatively, or neutrally charged depending on pH of their buffer solution and ionization conditions. To detect sialoglycopeptides, a negative-ion mode mass spectrometry may be applied with a minimal loss of sialic acids, although the positively charged or neutral glycopeptides may be excluded. Alternatively, the sialyl glycopeptides can be identified using positive-ion mode analysis by doping a high concentration of sodium salts to the analytes...
April 12, 2018: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29651207/protective-effect-of-allyl-isothiocyanate-on-glycoprotein-components-in-7-12-dimethylbenz-a-anthracene-induced-mammary-carcinoma-in-rats
#14
Thangarasu Rajakumar, Pachaiappan Pugalendhi, Subbaiyan Thilagavathi
The present study aimed to investigate the protective effect of allyl isothiocyanate (AITC) on glycoprotein components in 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female Sprague-Dawley rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near mammary gland. The levels of glycoprotein components such as hexose, hexosamine and sialic acid were analyzed colorimetrically in plasma, mammary and liver tissues. We observed an increased levels of glycoprotein components in plasma, mammary and liver tissues in cancer bearing rats...
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29624120/theoretical-investigations-and-density-functional-theory-based-probe-of-the-affinity-interaction-of-saccharide-ligands-with-extra-cellular-sialic-acid-residues
#15
Anjali Patel, Sanjay Tiwari, Prafulla K Jha
Changes in glycosylation pattern leads to malignant transformations among the cells. In combination with upregulated actions of sialyltransferases, it ultimately leads to differential expression of sialic acid (SA) at cell surface. Given its negative charge and localization to extracellular domain, SA has been exploited as a target for the development of targeted theranostics using approaches, such as, cationization and appending recognition saccharides on carrier surface. In this study, we have performed quantum mechanical calculations based on density functional theory (DFT) to study the interaction of saccharides with extracellular SA...
April 6, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29623903/single-particle-fusion-of-influenza-viruses-reveals-complex-interactions-with-target-membranes
#16
Guus van der Borg, Scarlett Braddock, Jelle Blijleven, Antoine van Oijen, Wouter Roos
The first steps in infection of influenza A virus is contact with the host cell membrane, with which it later fuses. The composition of the target bilayer exerts a complex influence on both fusion efficiency and time. Here, an in vitro, single-particle approach is used to study this effect. Using total internal reflection fluorescence (TIRF) microscopy and a microfluidic flow cell, the hemifusion of single virions is visualized. Hemifusion efficiency and kinetics are studied while altering target bilayer cholesterol content and sialic-acid donor...
April 6, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29619625/effects-of-plasma-glycosyltransferase-on-the-abo-h-blood-group-antigens-of-human-von-willebrand-factor
#17
Taiki Kano, Kazunao Kondo, Jiharu Hamako, Fumio Matsushita, Kazuya Sakai, Taei Matsui
Von Willebrand factor (VWF) is one of the plasma protein carrying ABO(H) blood group antigens, but the combining process of these antigens is not clear. In the present study, we examined whether plasma glycosyltransferase affects the blood group antigens on VWF. VWF expressing H-antigen (H-VWF) from blood group O and bovine serum albumin conjugated with H-antigen (H-BSA) were incubated with recombinant α1-3-N-acetylgalactosaminyltransferase (rA-transferase) and A-plasma with or without an additional UDP-GalNAc...
April 4, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29619343/alterations-of-the-human-skin-n-and-o-glycome-in-basal-cell-carcinoma-and-squamous-cell-carcinoma
#18
Uwe Möginger, Sonja Grunewald, René Hennig, Chu-Wei Kuo, Falko Schirmeister, Harald Voth, Erdmann Rapp, Kay-Hooi Khoo, Peter H Seeberger, Jan C Simon, Daniel Kolarich
The glycome of one of the largest and most exposed human organs, the skin, as well as glycan changes associated with non-melanoma skin cancers have not been studied in detail to date. Skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are among the most frequent types of cancers with rising incidence rates in the aging population. We investigated the healthy human skin N - and O -glycome and its changes associated with BCC and SCC. Matched patient samples were obtained from frozen biopsy and formalin-fixed paraffin-embedded tissue samples for glycomics analyses using two complementary glycomics approaches: porous graphitized carbon nano-liquid chromatography electro spray ionization tandem mass spectrometry and capillary gel electrophoresis with laser induced fluorescence detection...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29618635/removal-of-sialic-acid-from-bull-sperm-decreases-motility-and-mucus-penetration-ability-but-increases-zona-pellucida-binding-and-polyspermic-penetration-in-vitro
#19
Beatriz Fernandez-Fuertes, Alfonso Blanco-Fernandez, Colm J Reid, Kieran Meade, S Fair, Pat Lonergan
This study tested the hypothesis that sperm sialic acid (Sia) is required to reach the site of fertilization, and that successful fertilization requires recognition of Sia from both the sperm and oocyte to occur. In addition, it has recently been reported that Siglecs (Sia-binding-immunoglobulin-like lectins) are present on the sperm surface. Thus, the possibility that the recognition of oocyte Sia was sperm-Siglec-mediated was also addressed. Sperm exposed to neuraminidase (NMase) exhibited lower overall and progressive motility, which translated to a decreased ability to swim through cervical mucus from cows in oestrus...
April 4, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29617676/glycosylation-of-human-iga-directly-inhibits-influenza-a-and-other-sialic-acid-binding-viruses
#20
Michael A Maurer, Larissa Meyer, Matteo Bianchi, Hannah L Turner, Ngoc P L Le, Marco Steck, Arkadiusz Wyrzucki, Vanessa Orlowski, Andrew B Ward, Max Crispin, Lars Hangartner
Immunoglobulin A (IgA) plays an important role in protecting our mucosal surfaces from viral infection, in maintaining a balance with the commensal bacterial flora, and in extending maternal immunity via breast feeding. Here, we report an additional innate immune effector function of human IgA molecules in that we demonstrate that the C-terminal tail unique to IgA molecules interferes with cell-surface attachment of influenza A and other enveloped viruses that use sialic acid as a receptor. This antiviral activity is mediated by sialic acid found in the complex N-linked glycans at position 459...
April 3, 2018: Cell Reports
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