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Sialic Acid

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https://www.readbyqxmd.com/read/28103033/design-synthesis-and-biological-evaluation-of-small-high-affinity-siglec-7-ligands-toward-novel-inhibitors-of-cancer-immune-evasion
#1
Horst Prescher, Martin Frank, Stephan Gütgemann, Elena Kuhfeldt, Astrid Schweizer, Lars Nitschke, Carsten Watzl, Reinhard Brossmer
Natural killer cells are able to directly lyse tumor cells, thereby participating in the immune surveillance against cancer. Unfortunately, many cancer cells use immune evasion strategies to avoid their eradication by the immune system. A prominent escape strategy of malignant cells is to camouflage themselves with Siglec-7 ligands, thereby recruiting the inhibitory receptor Siglec-7 expressed on the NK cell surface which subsequently inhibits NK-cell-mediated lysis. Here we describe the synthesis and evaluation of the first, high-affinity low molecular weight Siglec-7 ligands to interfere with cancer cell immune evasion...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28101903/development-and-characterization-of-anti-glycopeptide-monoclonal-antibodies-against-human-podoplanin-using-glycan-deficient-cell-lines-generated-by-crispr-cas9-and-talen
#2
Mika K Kaneko, Takuro Nakamura, Ryusuke Honma, Satoshi Ogasawara, Yuki Fujii, Shinji Abe, Michiaki Takagi, Hiroyuki Harada, Hiroyoshi Suzuki, Yasuhiko Nishioka, Yukinari Kato
Human podoplanin (hPDPN), which binds to C-type lectin-like receptor-2 (CLEC-2), is involved in platelet aggregation and cancer metastasis. The expression of hPDPN in cancer cells or cancer-associated fibroblasts indicates poor prognosis. Human lymphatic endothelial cells, lung-type I alveolar cells, and renal glomerular epithelial cells express hPDPN. Although numerous monoclonal antibodies (mAbs) against hPDPN are available, they recognize peptide epitopes of hPDPN. Here, we generated a novel anti-hPDPN mAb, LpMab-21...
January 19, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28100988/simultaneous-analyses-of-n-linked-and-o-linked-glycans-of-ovarian-cancer-cells-using-solid-phase-chemoenzymatic-method
#3
Shuang Yang, Naseruddin Höti, Weiming Yang, Yang Liu, Lijun Chen, Shuwei Li, Hui Zhang
BACKGROUND: Glycans play critical roles in a number of biological activities. Two common types of glycans, N-linked and O-linked, have been extensively analyzed in the last decades. N-glycans are typically released from glycoproteins by enzymes, while O-glycans are released from glycoproteins by chemical methods. It is important to identify and quantify both N- and O-linked glycans of glycoproteins to determine the changes of glycans. METHODS: The effort has been dedicated to study glycans from ovarian cancer cells treated with O-linked glycosylation inhibitor qualitatively and quantitatively...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28096183/pneumococcal-neuraminidase-a-nana-promotes-biofilm-formation-and-synergizes-with-influenza-a-virus-in-nasal-colonization-and-middle-ear-infection
#4
John T Wren, Lance K Blevins, Bing Pang, Ankita Basu Roy, Melissa B Oliver, Jennifer L Reimche, Jessie E Wozniak, Martha A Alexander-Miller, W Edward Swords
Even in the vaccine era, Streptococcus pneumoniae (pneumococcus) remains a leading cause of otitis media, a significant public health burden, in large because of its high prevalence of nasal colonization in children. The primary pneumococcal neuraminidase NanA, which is a sialidase that catalyzes the cleavage of terminal sialic acids from host glycoconjugates, is involved in both of these processes. Coinfection with influenza A virus, which also expresses a neuraminidase, exacerbates nasal colonization and disease by S...
January 17, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28096130/early-life-nutrition-and-neurodevelopment-use-of-the-piglet-as-a-translational-model
#5
REVIEW
Austin T Mudd, Ryan N Dilger
Optimal nutrition early in life is critical to ensure proper structural and functional development of infant organ systems. Although pediatric nutrition historically has emphasized research on the relation between nutrition, growth rates, and gastrointestinal maturation, efforts increasingly have focused on how nutrition influences neurodevelopment. The provision of human milk is considered the gold standard in pediatric nutrition; thus, there is interest in understanding how functional nutrients and bioactive components in milk may modulate developmental processes...
January 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28095357/establishment-of-a-fluorescence-based-method-to-evaluate-endocytosis-of-desialylated-glycoproteins-in-vitro
#6
Cheng Luo, Song Chen, Na Xu, Wen Bo Sai, Wei Zhao, Ying Chun Li, Xiao Jing Hu, Hong Tian, Xiang Dong Gao, Wen Bing Yao
Insufficient sialylation can result in rapid clearance of therapeutic glycoproteins by intracellular degradation, which is mainly mediated by asialoglycoprotein receptors (ASGPRs) on hepatic cells. In contrast, for glycoproteins, a long half-life is often related to high level of terminal sialic acid. These could be extremely important for insufficient sialylated biomedicines in clinic, and development of therapeutic glycoproteins in laboratory. However, how the desialylated glycoproteins are removed and how to evaluate the ASGPRs mediated endocytosis in vitro needs further investigate...
January 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28091531/tnf-%C3%AE-regulates-the-proteolytic-degradation-of-st6gal-1-and-endothelial-cell-cell-junctions-through-upregulating-expression-of-bace1
#7
Xiao Deng, Jun Zhang, Yan Liu, Linmu Chen, Chao Yu
Endothelial dysfunction and monocyte adhesion to vascular endothelial cells are two critical steps in atherosclerosis development, and emerging evidence suggests that protein sialylation is involved in these processes. However, the mechanism underlying this phenomenon remains incompletely elucidated. In this study, we demonstrated that treatment with the proinflammatory cytokine TNF-α disrupted vascular endothelial cell-cell tight junctions and promoted monocyte endothelial cell adhesion. Western blotting and Sambucus nigra lectin (SNA) blotting analyses revealed that TNF-α treatment decreased α-2, 6-sialic acid transferase 1 (ST6Gal-I) levels and downregulated VE-Cadherin α-2, 6 sialylation...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090561/diversity-in-rotavirus-host-glycan-interactions-a-sweet-spectrum
#8
REVIEW
Sasirekha Ramani, Liya Hu, B V Venkataram Prasad, Mary K Estes
Interaction with cellular glycans is a critical initial step in the pathogenesis of many infectious agents. Technological advances in glycobiology have expanded the repertoire of studies delineating host glycan-pathogen interactions. For rotavirus, the VP8* domain of the outer capsid spike protein VP4 is known to interact with cellular glycans. Sialic acid was considered the key cellular attachment factor for rotaviruses for decades. Although this is true for many rotavirus strains causing infections in animals, glycan array screens show that many human rotavirus strains bind nonsialylated glycoconjugates, called histo-blood group antigens, in a strain-specific manner...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28089756/glycan-alteration-imparts-cellular-resistance-to-a-membrane-lytic-anticancer-peptide
#9
Ken Ishikawa, Scott H Medina, Joel P Schneider, Amar J S Klar
Although resistance toward small-molecule chemotherapeutics has been well studied, the potential of tumor cells to avoid destruction by membrane-lytic compounds remains unexplored. Anticancer peptides (ACPs) are a class of such agents that disrupt tumor cell membranes through rapid and non-stereospecific mechanisms, encouraging the perception that cellular resistance toward ACPs is unlikely to occur. We demonstrate that eukaryotic cells can, indeed, develop resistance to the model oncolytic peptide SVS-1, which preferentially disrupts the membranes of cancer cells...
January 9, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28089228/intraplantar-injection-of-sialidase-reduces-mechanical-allodynia-during-inflammatory-pain
#10
Shun Watanabe, Takashi Iwai, Mitsuo Tanabe
Sialic acids are highly charged glycoresidues that are attached to glycoproteins or glycosphingolipids, and they are associated with various biological functions. Gangliosides, sialic acid-containing glycosphingolipids, are abundant in neural tissues and play important roles in the nervous system. Previous studies revealed that peripheral gangliosides are involved in nociceptive behavior and hyperalgesia. These observations prompted us to determine whether the sialic acid-cleaving enzyme sialidase affects pain signaling...
January 3, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28087363/membrane-restructuring-following-in-situ-sialidase-digestion-of-gangliosides-complex-model-bilayers-by-synchrotron-radiation-reflectivity
#11
Valeria Rondelli, Paola Brocca, Giovanna Fragneto, Jean Daillant, Cristina Tringali, Laura Cantu', Elena Del Favero
Synchrotron radiation reflectometry was used to access the transverse structure of model membranes under the action of the human sialidase NEU2, down to the Ångström length scale. Model membranes were designed to mimic the lipid composition of so-called Glycosphingolipids Enriched Microdomains (GEMs), which are membrane platforms specifically enriched in cholesterol and sphingolipids, where also typical signalling molecules are hosted. Gangliosides, glycosphingolipids containing one or more sialic acid residues, are asymmetrically embedded in GEMs, in the outer membrane leaflet...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28076802/peldor-spectroscopy-reveals-two-defined-states-of-a-sialic-acid-trap-transporter-sbp-in-solution
#12
Janin Glaenzer, Martin F Peter, Gavin H Thomas, Gregor Hagelueken
The tripartite ATP-independent periplasmic (TRAP) transporters are a widespread class of membrane transporters in bacteria and archaea. Typical substrates for TRAP transporters are organic acids including the sialic acid N-acetylneuraminic acid. The substrate binding proteins (SBP) of TRAP transporters are the best studied component and are responsible for initial high-affinity substrate binding. To better understand the dynamics of the ligand binding process, pulsed electron-electron double resonance (PELDOR, also known as DEER) spectroscopy was applied to study the conformational changes in the N-acetylneuraminic acid-specific SBP VcSiaP...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28072827/comprehensive-n-glycan-profiling-of-cetuximab-biosimilar-candidate-by-np-hplc-and-maldi-ms
#13
Sheng Liu, Wenjie Gao, Yao Wang, Zhenyu He, Xiaojun Feng, Bi-Feng Liu, Xin Liu
Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS)...
2017: PloS One
https://www.readbyqxmd.com/read/28069944/soluble-klotho-binds-monosialoganglioside-to-regulate-membrane-microdomains-and-growth-factor-signaling
#14
George Dalton, Sung-Wan An, Saif I Al-Juboori, Nicole Nischan, Joonho Yoon, Evgenia Dobrinskikh, Donald W Hilgemann, Jian Xie, Kate Luby-Phelps, Jennifer J Kohler, Lutz Birnbaumer, Chou-Long Huang
Soluble klotho, the shed ectodomain of the antiaging membrane protein α-klotho, is a pleiotropic endocrine/paracrine factor with no known receptors and poorly understood mechanism of action. Soluble klotho down-regulates growth factor-driven PI3K signaling, contributing to extension of lifespan, cardioprotection, and tumor inhibition. Here we show that soluble klotho binds membrane lipid rafts. Klotho binding to rafts alters lipid organization, decreases membrane's propensity to form large ordered domains for endocytosis, and down-regulates raft-dependent PI3K/Akt signaling...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28064019/the-random-co-polymer-glatiramer-acetate-rapidly-kills-primary-human-leukocytes-through-sialic-acid-dependent-cell-membrane-damage
#15
Stig Hill Christiansen, Xianwei Zhang, Kristian Juul-Madsen, Michael Lykke Hvam, Brian Stougaard Vad, Manja Annette Behrens, Ida Lysgaard Thygesen, Babak Jalilian, Jan Skov Pedersen, Kenneth A Howard, Daniel E Otzen, Thomas Vorup-Jensen
The formulation glatiramer acetate (GA) is widely used in therapy of multiple sclerosis. GA consists of random copolymers of four amino acids, in ratios that produce a predominantly positive charge and an amphipathic character. With the extraordinary complexity of the drug, several pharmacological modes-of-action were suggested, but so far none, which rationalizes the cationicity and amphipathicity as part of the mode-of-action. Here, we report that GA rapidly kills primary human T lymphocytes and, less actively, monocytes...
January 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28063409/tinospora-cordifolia-extract-attenuates-cadmium-induced-biochemical-and-histological-alterations-in-the-heart-of-male-wistar-rats
#16
Lohanathan Bharathi Priya, Rathinasamy Baskaran, Pitchai Elangovan, Velumani Dhivya, Chih-Yang Huang, Viswanadha Vijaya Padma
Persistence of cadmium (Cd) in the environment causes serious ecological problems. Tinospora cordifolia is a medicinal herb used in Ayurveda for treating various metabolic disorders and toxic conditions. The present study investigates the protective effect of T. cordifolia stem methanolic extract (TCME) on a heavy metal, Cd-induced cardiotoxicity in male Wistar rats. Male albino Wistar rats were divided into four groups (n=6). The animals after treatment for 28days with Cd and TCME were analysed for biochemical and histological changes in the serum and heart tissues...
January 4, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28062483/the-sialic-acid-to-urea-ratio-as-a-measure-of-airway-surface-hydration
#17
Charles R Esther, David B Hill, Brian Button, Shuai Shi, Corey M Jania, Elizabeth A Duncan, Claire M Doerschuk, Gang Chen, Sarath Ranganathan, Stephen Michael Stick, Richard C Boucher
INTRODUCTION: Although airway mucus dehydration is key to pathophysiology of cystic fibrosis (CF) and other airways diseases, measuring mucus hydration is challenging. We explored a robust method to estimate mucus hydration using sialic acid as a marker for mucin content. METHODS: Terminal sialic acid residues from mucins were cleaved by acid hydrolysis from airway samples, and concentrations of sialic acid, urea, and other biomarkers analyzed using mass spectrometry...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28056926/edible-bird-s-nest-modulate-intracellular-molecular-pathways-of-influenza-a-virus-infected-cells
#18
Amin Haghani, Parvaneh Mehrbod, Nikoo Safi, Fadzilah A'ini Abd Kadir, Abdul Rahman Omar, Aini Ideris
BACKGROUND: Edible Bird's Nest (EBN) as a popular traditional Chinese medicine is believed to have health enhancing and antiviral activities against influenza A virus (IAV); however, the molecular mechanism behind therapeutic effects of EBN is not well characterized. METHODS: In this study, EBNs that underwent different enzymatic preparation were tested against IAV infected cells. 50% cytotoxic concentration (CC50) and 50% inhibitory concentration (IC50) of the EBNs against IAV strain A/Puerto Rico/8/1934(H1N1) were determined by HA and MTT assays...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28054185/characterization-of-human-hybrid-cell-line-f2n78-through-a-comparison-of-culture-performances-and-protein-qualities
#19
Joon Serk Seo, Byung Sub Min, Yeon Jung Kim, Jong Moon Cho, Gi-Seong Kwon, Byeong-Pil Lim, Shin-Jae Chang, Dong-Il Kim
OBJECTIVES: To evaluate the characteristics of a novel human cell line, F2N78, including growth performance, physicochemical properties, and biological activity via direct comparison with CHO cells. RESULTS: The culture performance and physicochemical properties of antibodies produced from F2N78 and CHO cells were compared. For charge variants, antibodies produced from F2N78 cells contained a greater acidic charge variants than CHO cells. Regarding main glycoforms, degree of galactosylation was 52% in CT-A produced from F2N78 cells compared to CHO cells (37%)...
January 4, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28053670/the-complete-genome-sequence-of-cronobacter-sakazakii-atcc-29544-t-a-food-borne-pathogen-isolated-from-a-child-s-throat
#20
Seongok Kim, You-Tae Kim, Hyunjin Yoon, Ju-Hoon Lee, Sangryeol Ryu
BACKGROUND: Cronobacter sakazakii is an emerging opportunistic pathogen that is associated with rare but life-threatening cases of severe diseases: meningitis, necrotizing enterocolitis, and sepsis in premature and full-term infants. However, the pathogenesis mechanism of this pathogen remains largely unknown. To determine its pathogenesis at the genomic level, the genome of C. sakazakii ATCC 29544(T) was completely sequenced and analyzed. RESULTS: The genomic DNA, containing a circular chromosome and three plasmids, is composed of 4,511,265 bp with a GC content of 56...
2017: Gut Pathogens
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