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Sialic Acid

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https://www.readbyqxmd.com/read/28346741/small-molecules-targeting-human-n-acetylmannosamine-kinase
#1
Stephan Hinderlich, Martin Neuenschwander, Paul-Robin Wratil, Andreas Oder, Michael Lisurek, Long D Nguyen, Jens Peter von Kries, Christian Hackenberger
N-Acetylmannosamine kinase (MNK) plays a key role in the biosynthesis of sialic acids and glycosylation of proteins. Sialylated glycoconjugates affect a large number of biological processes, including immune modulation and cancer transformation. For the search of effective inhibitors of MNK we applied high-throughput screening of drug-like small molecules. Applying different orthogonal assays for their validation we identified four potential MNK-specific inhibitors with IC50 values in the low micromolar range...
March 27, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28344780/abnormal-glycosylation-in-joubert-syndrome-type-10
#2
Megan S Kane, Mariska Davids, Michelle R Bond, Christopher J Adams, Megan E Grout, Ian G Phelps, Diana R O'Day, Jennifer C Dempsey, Xeuli Li, Gretchen Golas, Gilbert Vezina, Meral Gunay-Aygun, John A Hanover, Dan Doherty, Miao He, May Christine V Malicdan, William A Gahl, Cornelius F Boerkoel
BACKGROUND: The discovery of disease pathogenesis requires systematic agnostic screening of multiple homeostatic processes that may become deregulated. We illustrate this principle in the evaluation and diagnosis of a 5-year-old boy with Joubert syndrome type 10 (JBTS10). He carried the OFD1 mutation p.Gln886Lysfs*2 (NM_003611.2: c.2656del) and manifested features of Joubert syndrome. METHODS: We integrated exome sequencing, MALDI-TOF mass spectrometry analyses of plasma and cultured dermal fibroblasts glycomes, and full clinical evaluation of the proband...
2017: Cilia
https://www.readbyqxmd.com/read/28344335/influenza-a-virus-hemagglutinin-and-neuraminidase-act-as-novel-motile-machinery
#3
Tatsuya Sakai, Shin I Nishimura, Tadasuke Naito, Mineki Saito
Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336455/targeted-delivery-of-epirubicin-to-tumor-associated-macrophages-by-sialic-acid-cholesterol-conjugate-modified-liposomes-with-improved-antitumor-activity
#4
Songlei Zhou, Ting Zhang, Bo Peng, Xiang Luo, Xinrong Liu, Ling Hu, Yang Liu, Donghua Di, Yanzhi Song, Yihui Deng
With the knowledge that the receptors of sialic acid are overexpressed on the surface of tumor-associated macrophages (TAMs), which play a crucial role in the tumor's progression and metastasis, a sialic acid-cholesterol conjugate (SA-CH) was synthesized and modified on the surface of epirubicin (EPI)-loaded liposomes (EPI-SAL) to improve the delivery of EPI to the TAMs. The liposomes were developed using remote loading technology via a pH gradient. The liposomes were evaluated for particle size, encapsulation efficiency, in vitro release, stability, in vitro cytotoxicity and pharmacokinetics...
March 20, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28335432/marine-lectins-dlfbl-and-hddsbl-fused-with-soluble-coxsackie-adenovirus-receptor-facilitate-adenovirus-infection-in-cancer-cells-but-have-different-effects-on-cell-survival
#5
Bingbing Wu, Shengsheng Mei, Lianzhen Cui, Zhenzhen Zhao, Jianhong Chen, Tao Wu, Gongchu Li
Cancer development and progression are usually associated with glycosylation change, providing prognostic and diagnostic biomarkers, as well as therapeutic targets, for various cancers. In this work, Dicentrarchus labrax fucose binding lectin (DlFBL) and Haliotis discus discus sialic acid binding lectin (HddSBL) were genetically fused with soluble coxsackie-adenovirus receptor (sCAR), and produced through a bacterial expression system. Results showed that recombinant sCAR-DlFBL not only facilitated adenovirus Ad-EGFP infection in K562/ADR and U87MG cells, but also enhanced the cytotoxicity of adenovirus harboring gene encoding Pinellia pedatisecta agglutinin (PPA) or DlFBL (Ad-PPA or Ad-DlFBL) on U87MG cells through inducing apoptosis...
March 14, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28327617/the-cell-surface-mucin-muc1-limits-the-severity-of-influenza-a-virus-infection
#6
J L McAuley, L Corcilius, H-X Tan, R J Payne, M A McGuckin, L E Brown
Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28325922/variability-in-h9n2-haemagglutinin-receptor-binding-preference-and-the-ph-of-fusion
#7
Thomas P Peacock, Donald J Benton, Jean-Remy Sadeyen, Pengxiang Chang, Joshua E Sealy, Juliet E Bryant, Stephen R Martin, Holly Shelton, John W McCauley, Wendy S Barclay, Munir Iqbal
H9N2 avian influenza viruses are primarily a disease of poultry; however, they occasionally infect humans and are considered a potential pandemic threat. Little work has been performed to assess the intrinsic biochemical properties related to zoonotic potential of H9N2 viruses. The objective of this study, therefore, was to investigate H9N2 haemagglutinins (HAs) using two well-known correlates for human adaption: receptor-binding avidity and pH of fusion. Receptor binding was characterized using bio-layer interferometry to measure virus binding to human and avian-like receptor analogues and the pH of fusion was assayed by syncytium formation in virus-infected cells at different pHs...
March 22, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28325905/evidence-for-c1q-mediated-crosslinking-of-cd33-lair-1-inhibitory-immunoreceptors-and-biological-control-of-cd33-lair-1-expression
#8
Myoungsun Son, Betty Diamond, Bruce T Volpe, Cynthia B Aranow, Meggan C Mackay, Frances Santiago-Schwarz
C1q collagen-like region (CLR) engaging and activating the LAIR-1 inhibitory immunoreceptor represents a non-complement mechanism for maintaining immune quiescence. Given the binding promiscuity of C1q's globular region (gC1q), we hypothesized that C1q concurrently associates with distinct inhibitory immunoreceptors to produce C1q-mediated modulatory networking. Like LAIR-1, CD33 inhibitory immunoreceptors are highly expressed on monocytes. Binding CD33 restricts cell activation/differentiation; however, natural ligands for CD33 remain elusive...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320965/deficiency-of-a-sulfotransferase-for-sialic-acid-modified-glycans-mitigates-alzheimer-s-pathology
#9
Zui Zhang, Yoshiko Takeda-Uchimura, Tahmina Foyez, Shiori Ohtake-Niimi, Narentuya, Hiroyasu Akatsu, Kazuchika Nishitsuji, Makoto Michikawa, Tony Wyss-Coray, Kenji Kadomatsu, Kenji Uchimura
We previously showed that microglial keratan sulfate (KS) was induced in amyotrophic lateral sclerosis. However, the functional roles of the glycan and its synthetic enzyme in neurodegenerative diseases, such as Alzheimer's disease (AD), a progressive disorder, are unclear. In our study, KS modified with sialic acids having a molecular mass of 125-220 kDa and the carbohydrate sulfotransferase GlcNAc6ST1 were up-regulated in the brains of two transgenic mouse models (J20 and Tg2576) and the brains of patients with AD...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28318221/crystal-structure-of-a-homogeneous-igg-fc-glycoform-with-the-n-glycan-designed-to-maximize-the-antibody-dependent-cellular-cytotoxicity
#10
Chia-Lin Chen, Jen-Chi Hsu, Chin-Wei Lin, Chia-Hung Wang, Ming-Hung Tsai, Chung-Yi Wu, Chi-Huey Wong, Che Ma
N-glycosylation on IgG modulates Fc conformation and effector functions. An IgG-Fc contains a human sialo-complex type (hSCT) glycan of biantennary structure with two α2,6-sialylations and without core-fucosylation is an optimized glycoform developed to enhance the antibody dependent cellular cytotoxicity (ADCC). hSCT modification not only enhances the binding affinity to Fc receptors in the presence of antigen, but also in some cases provides gain-of-function effector activity. We used enzymatic glyco-engineering to prepare an IgG-Fc with homogeneous hSCT attached to each CH2 domain, and solved its crystal structure...
March 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28318083/dienophile-modified-mannosamine-derivatives-for-metabolic-labeling-of-sialic-acids-a-comparative-study
#11
Jeremias E G A Dold, Jessica Pfotzer, Anne-Katrin Späte, Valentin Wittmann
Sialic acids play an important role in numerous cell adhesion processes and sialylation levels are known to be altered under certain pathogenic conditions such as cancer. Metabolic glycoengineering with mannosamine derivatives is a convenient way to introduce non-natural chemical reporter groups into sialylated glycoconjugates offering the opportunity to label sialic acids using bioorthogonal ligation chemistry. The labeling intensity not only depends on the rate of the ligation reaction but also on the extent to which the natural sialic acids are replaced by the modified ones, i...
March 20, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28302328/experimental-pseudomonas-aeruginosa-mediated-rhino-sinusitis-in-mink
#12
S Kirkeby, A S Hammer, N Høiby, C M Salomonsen
OBJECTIVES: The nasal and sinus cavities in children may serve as reservoirs for microorganisms that cause recurrent and chronic lung infections. This study evaluates whether the mink can be used as an animal model for studying Pseudomonas aeruginosa mediated rhino-sinusitis since there is no suitable traditional animal model for this disease. METHODS: Nasal tissue samples from infected and control mink were fixed in formalin, demineralized, and embedded in paraffin...
December 27, 2016: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28295942/gangliosides-structure-biosynthesis-analysis-and-roles-in-cancer
#13
Sophie Groux-Degroote, Yann Guérardel, Philippe Delannoy
Gangliosides are acidic glycosphingolipids containing one or more sialic acid residues. They are essential compounds at the outer leaflet of the plasma membrane where they interact with phospholipids, cholesterol and transmembrane proteins, forming lipid rafts. They are involved in cell adhesion, proliferation and recognition processes, as well as in the modulation of signal transduction pathways. These functions are mainly supported by the glycan moiety and changes in the structure of gangliosides occur under pathological conditions, particularly in neuro-ectoderm-derived cancers...
March 15, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28288142/serine-hydroxymethyl-transferase-1-stimulates-pro-oncogenic-cytokine-expression-through-sialic-acid-to-promote-ovarian-cancer-tumor-growth-and-progression
#14
R Gupta, Q Yang, S K Dogra, N Wajapeyee
High-grade serous (HGS) ovarian cancer accounts for 90% of all ovarian cancer-related deaths. However, factors that drive HGS ovarian cancer tumor growth have not been fully elucidated. In particular, comprehensive analysis of the metabolic requirements of ovarian cancer tumor growth has not been performed. By analyzing The Cancer Genome Atlas mRNA expression data for HGS ovarian cancer patient samples, we observed that six enzymes of the folic acid metabolic pathway were overexpressed in HGS ovarian cancer samples compared with normal ovary samples...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28286312/aberrant-ganglioside-composition-in-glioblastoma-multiforme-and-peritumoral-tissue-a-mass-spectrometry-characterization
#15
Dragana Fabris, Marko Rožman, Tomislav Sajko, Željka Vukelić
Tumor cells are characterized by aberrant glycosylation of the cell surface glycoconjugates. Gangliosides are sialylated glycosphingolipids highly abundant in neural tissue and considered as tumor markers and therapeutic targets. In this study, a detailed characterization of native ganglioside mixtures from glioblastoma multiforme, corresponding peritumoral tissue and healthy human brain was performed using mass spectrometry and high performance thin layer chromatography in order to elucidate their roles as tumor-associated antigens...
March 9, 2017: Biochimie
https://www.readbyqxmd.com/read/28284612/pathogenicity-and-transmission-of-triple-reassortant-h3n2-swine-influenza-a-viruses-is-attenuated-following-turkey-embryo-propagation
#16
Shobana Raghunath, Raghavendra Sumanth Pudupakam, Jagadeeswaran Deventhiran, Rahul Tevatia, Tanya Leroith
Genetic lineages of swine influenza A viruses (SIVs) have recently been established in Turkeys in the United States. To identify molecular determinants that are involved in virulence and transmission of SIVs to Turkeys, we sequentially passaged two triple reassortant H3N2 SIV isolates from Minnesota in ten day old specific-pathogen free (SPF) Turkey embryos and tested them in seven-day old Turkey poults. We found that SIV replication in Turkey embryos led to minimal mutations in and around the receptor binding and antigenic sites of the HA molecule, while other gene segments were unchanged...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28283679/the-immunological-function-of-cd52-and-its-targeting-in-organ-transplantation
#17
REVIEW
Yang Zhao, Huiting Su, Xiaofei Shen, Junfeng Du, Xiaodong Zhang, Yong Zhao
INTRODUCTION: CD52 (Campath-1 antigen), a glycoprotein of 12 amino acids anchored to glycosylphosphatidylinositol, is widely expressed on the cell surface of immune cells, such as mature lymphocytes, natural killer cells (NK), eosinophils, neutrophils, monocytes/macrophages, and dendritic cells (DCs). The anti-CD52 mAb, alemtuzumab, was used widely in clinics for the treatment of patients such as organ transplantation. In the present manuscript, we will briefly summarize the immunological function of CD52 and discuss the application of anti-CD52 mAb in transplantation settings...
March 10, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28282148/alterations-in-the-salivary-proteome-and-n-glycome-of-sj%C3%A3-gren-s-syndrome-patients
#18
Steven C Hall, Maria E Hassis, Katherine E Williams, Matthew E Albertolle, Akraporn Prakobphol, Andrew B Dykstra, Megan Laurance, Katherine Ona, Richard K Niles, Namrata Prasad, Matthew Gormley, Caroline Shiboski, Lindsey A Criswell, H Ewa Witkowska, Susan J Fisher
We used isobaric mass tagging (iTRAQ) and lectin affinity capture mass spectrometry (MS)-based workflows for global analyses of parotid saliva (PS) and whole saliva (WS) samples obtained from patients diagnosed with primary Sjögren's Syndrome (pSS) who were enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) as compared with two control groups. The iTRAQ analyses revealed up- and down-regulation of numerous proteins that could be involved in the disease process (e.g., histones) or attempts to mitigate the ensuing damage (e...
March 24, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28281252/plasmonics-based-detection-of-virus-using-sialic-acid-functionalized-gold-nanoparticles
#19
Changwon Lee, Peng Wang, Marsha A Gaston, Alison A Weiss, Peng Zhang
Biosensor for the detection of virus was developed by utilizing plasmonic peak shift phenomenon of the gold nanoparticles and viral infection mechanism of hemagglutinin on virus and sialic acid on animal cells. The plasmonic peak of the colloidal gold nanoparticles changes with the aggregation of the particles due to the plasmonic interaction between nearby particles and the color of the colloidal nanoparticle solution changes from wine red to purple. Sialic acid reduced and stabilized colloidal gold nanoparticle aggregation is induced by the addition of viral particles in the solution due to the hemagglutinin-sialic acid interaction...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28280963/development-of-an-in-vitro-bioassay-for-recombinant-human-erythropoietin-rhuepo-based-on-proliferative-stimulation-of-an-erythroid-cell-line-and-analysis-of-sialic-acid-dependent-microheterogeneity-ut-7-cell-bioassay
#20
Manoj Kumar Metta, Vasavi Malkhed, Srinivasan Tantravahi, Uma Vuruputuri, Rajkumar Kunaparaju
Determination of biological activity and its comparison with clinical behavior is important in the quality assessment of therapeutic glycoproteins. In vivo studies are usually employed for evaluating bioactivity of these glycomolecules. However, alternative methods are required to simplify the bioassay and avoid ethical issues associated with in vivo studies. Negatively charged sialic acid residues are known to be critical for in vivo bioactivity of rHuEPO. To address this need, we employed the human acute myeloid leukemia cell line UT-7 for the determination of proliferative stimulation induced by rHuEPO...
March 9, 2017: Protein Journal
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