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https://www.readbyqxmd.com/read/29457892/boronic-acid-catalyzed-regio-and-1-2-cis-stereoselective-glycosylation-of-unprotected-sugar-acceptors-via-s-n-i-type-mechanism
#1
Masamichi Tanaka, Akira Nakagawa, Nobuya Nishi, Kiyoko Iijima, Ryuichi Sawa, Daisuke Takahashi, Kazunobu Toshima
Regio- and 1,2-cis-stereoselective chemical glycosylation of unprotected glycosyl acceptors has been in great demand for the efficient synthesis of natural glycosides. However, simultaneously regulating these selectivities has been a long-standing problem in synthetic organic chemistry. In nature, glycosyl transferases catalyze regioselective 1,2-cis-glycosylations via the SN i mechanism, yet no useful chemical glycosylations based on this mechanism have been developed. In this paper, we report a highly regio- and 1,2-cis-stereoselective SN i-type glycosylation of 1,2-anhydro donors and unprotected sugar acceptors using p-nitrophenylboronic acid (10e) as a catalyst in the presence of water under mild conditions...
February 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29457654/chemoselective-glycosylation-of-peptides-via-s-alkylation-reaction
#2
Stefania De Luca, Enrica Calce, Valeria Manchise, Michele Saviano, Giuseppe Digilio
An efficient and fast procedure in execution for synthesizing S-linked glycopeptides is reported. It uses activated molecular sieves as a base to promote the selective S-alkylation of readily prepared cysteine-containing peptides, upon reaction of appropriate glycosyl halides. Due to the very mild conditions employed, the chemoselective linkage of the electrophilic sugar with a peptide sulfhydryl group occurred in a satisfactory yield, allowing the incorporation of mono and disaccharide moieties. The sugar-peptide conjugates obtained from α-D-glycosyl derivatives adopt a beta-S-conformation, indicating the high stereoselectivity of the substitution reaction...
February 19, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29457629/antibody-glycoengineering-strategies-in-mammalian-cells
#3
Qiong Wang, Cheng-Yu Chung, Sandra Chough, Michael J Betenbaugh
As a key parameter impacting functional and structural heterogeneity, protein glycosylation is a critical quality attribute for antibody biotherapeutic manufacturing. The glycan patterns on recombinant antibodies, particularly on the conserved fragment crystallizable (Fc) region, can have significant effects on an antibody's functional activities including clearance rate, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and anti-inflammatory activity. In this review, we examined specific glycan attachments (fucosylation, sialylation, galactosylation, oligo-mannose and bisecting glycans) and their importance to antibody properties...
February 19, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29457375/evidence-for-alternate-modes-of-b-cell-activation-involving-fab-acquired-n-glycosylations-in-antibody-secreting-cells-infiltrating-the-labial-salivary-glands-of-sj%C3%A3-gren-s-syndrome-patients
#4
Kristi A Koelsch, Joshua Cavett, Kenneth Smith, Jacen S Moore, Sylvain D Lehoux, Nan Jia, Tim Mather, Syed M S Quadri, Astrid Rasmussen, C Erick Kaufman, David M Lewis, Lida Radfar, Teresa A Scordino, Christopher J Lessard, Biji T Kurien, Richard D Cummings, Judith A James, Kathy L Sivils, A Darise Farris, R Hal Scofield
OBJECTIVE: To better understand the role of B cells, potential mechanisms for their aberrant activation, and the production of autoantibodies in the pathogenesis of Sjögren's Syndrome (SS), we explored selection pressures and N-glycosylation acquired by somatic mutation (acN-glyc) in the immunoglobulin (Ig) variable regions (V-regions) of antibody secreting cells (ASCs) isolated from the minor salivary glands of SS patients and non-SS controls with sicca symptoms. METHODS: We report a novel method to produce and characterize recombinant monoclonal antibodies (mAbs) from SS patient and control labial salivary gland single-cell sorted ASC infiltrates that can be utilized to concurrently probe any other expressed genes...
February 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29457265/the-role-of-type-2-diabetes-mellitus-on-hypertensive-related-aortic-stiffness
#5
Edoardo Sciatti, Enrico Vizzardi, Assunta Castiello, Francesca Valentini, Ivano Bonadei, Sandro Gelsomino, Roberto Lorusso, Marco Metra
BACKGROUND: Hypertension is strongly related to arterial stiffness in a cause-effect fashion. Diabetes mellitus is also thought to determine vascular damage, mostly by means of advanced glycosylation end-products (AGEs). Aim of our study was to study the role of type 2 diabetes mellitus (T2DM) as regard ascending aortic elastic properties in hypertensive patients. METHODS: We prospectively enrolled outpatients with hypertension (n = 99) and type 2 diabetes mellitus plus hypertension (n = 42) without cardiovascular events...
February 19, 2018: Echocardiography
https://www.readbyqxmd.com/read/29456697/relationship-between-fat-mass-and-obesity-associated-gene-expression-and-type-2-diabetes-mellitus-severity
#6
Qiuling Wang, Jinhuan Wang, Haixia Lin, Xuechen Huo, Qiaoling Zhu, Min Zhang
This study sought to investigate any correlation between fat mass and obesity-associated gene (FTO) expression and the severity of type 2 diabetes mellitus (T2DM). In total 110 patients newly diagnosed with T2DM in the outpatient department of Yantai Yuhuangding Hospital between September 2016 and March 2017 were selected as study subjects and were divided into severe (58 cases) and mild groups (52 cases) according to T2DM severity. Patients in the severe group were followed up for 12 weeks. An additional 60 healthy individuals were selected to serve as the normal control group...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456013/oxidation-pattern-of-curdlan-with-tempo-mediated-system
#7
Rong Tang, Jie Hao, Ruijie Zong, Fangxia Wu, Yangyang Zeng, Zhenqing Zhang
In this study, the TEMPO-mediated (TEMPO/NaBr/NaClO) oxidation pattern of curdlan was investigated through comprehensively structural analysis of the corresponding oxidized products. During the structural analysis, infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography tandem multiple angle laser scattering (GPC-MALS) and ultra-high performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UHPLC-Q/TOF-MS) were applied. As a result, the homogenous β1-3 polyglucuronic acids (MW, 49...
April 15, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29455388/heterologous-expression-of-rtshyal-1-the-first-recombinant-hyaluronidase-of-scorpion-venom-produced-in-pichia-pastoris-system
#8
Fernanda Gobbi Amorim, Johara Boldrini-França, Karla de Castro Figueiredo Bordon, Iara Aimê Cardoso, Edwin De Pauw, Loïc Quinton, Simone Kashima, Eliane Candiani Arantes
In general, hyaluronidases have a broad potential application on medicine and esthetics fields. Hyaluronidases from animal venoms cleave hyaluronan present in the extracellular matrix, acting as spreading factors of toxins into the tissues of the victim. However, the in-depth characterization of hyaluronidase from animal venoms has been neglected due to its instability and low concentration in the venom, which hamper its isolation. Thus, heterologous expression of hyaluronidase acts as a biotechnological tool in the obtainment of enough amounts of the enzyme for structural and functional studies...
February 17, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29454942/cloning-molecular-modeling-and-characterization-of-acidic-cellulase-from-buffalo-rumen-and-its-applicability-in-saccharification-of-lignocellulosic-biomass
#9
Tripti Dadheech, Ravi Shah, Ramesh Pandit, Ankit Hinsu, Prakram Singh Chauhan, Subhash Jakhesara, Anju Kunjadiya, Dharamshibhai Rank, Chaitanya Joshi
Cellulase hydrolyses the cellulose by cleaving the β-1,4-linkages to produce mono-, oligo- and shorter polysaccharide units. These enzymes have applications in various industries such as pulp and paper, laundry, food and feed, textile, brewing industry and in biofuel production. In the present study we have cloned acid-cellulase gene (Cel-1) from the fosmid library of buffalo rumen metagenomic DNA and functionally expressed it in Escherichia coli. The ORF encoding cellulase consisted of 1176-bp, corresponding to protein of 391 amino acid and has catalytic domain belonging to glycosyl hydrolase family 5...
February 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29454724/-silent-diabetes-and-clinical-outcome-after-treatment-with-contemporary-drug-eluting-stents-the-bio-resort-silent-diabetes-study
#10
Clemens von Birgelen, Marlies M Kok, Naveed Sattar, Paolo Zocca, Cees Doelman, Gert D Kant, Marije M Löwik, Liefke C van der Heijden, Hanim Sen, K Gert van Houwelingen, Martin G Stoel, J Hans W Louwerenburg, Marc Hartmann, Frits H A F de Man, Gerard C M Linssen, Carine J M Doggen, Kenneth Tandjung
OBJECTIVES: This study sought to assess the prevalence and clinical impact of silent diabetes and pre-diabetes in "nondiabetic" percutaneous coronary intervention (PCI) all-comers. BACKGROUND: Patients with undetected and thus untreated (silent) diabetes may have higher event risks after PCI with contemporary drug-eluting stents (DES). METHODS: The BIO-RESORT Silent Diabetes study, performed at Thoraxcentrum Twente, is a substudy of the randomized multicenter BIO-RESORT (BIOdegradable Polymer and DuRable Polymer Drug-eluting Stents in an All COmeRs PopulaTion) trial (NCT01674803)...
February 8, 2018: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29454248/stereocontrolled-synthesis-of-oleanolic-saponin-ladyginoside-a-isolated-from-ladyginia-bucharica
#11
Matylda Stefaniak, Grzegorz Łopatkiewicz, Magdalena Antkowiak, Jacek Mlynarski
Efficient stereocontrolled synthesis of ladyginoside A isolated from Ladyginia bucharica is described. The presented methodology bases on the β-selective glycosylation to construct oleanate-3-O-β-glycoside from selectively protected d-cellobiose comprising desired β-linkage in carbohydrate unit. By using this procedure, dimethyl ester of ladyginoside A (1) (methyl oleanate 3-O-(β-d-glucopyranosyl)-(1 → 4)-β-d-glucuronide methyl ester) was obtained in 16% overall yield. Elaborated synthesis is also demonstrated as useful methodology en route to saponin 2 with additional glucose unit, namely 3-O-[β-d-glucopyranosyl-(1 → 4)-β-d-glucuronide] oleanolic acid 28-O-β-d-glucopyranosyl ester...
February 8, 2018: Carbohydrate Research
https://www.readbyqxmd.com/read/29453742/the-effect-of-physical-activity-interventions-on-glycosylated-haemoglobin-hba-1c-in-non-diabetic-populations-a-systematic-review-and-meta-analysis
#12
REVIEW
Iván Cavero-Redondo, Bárbara Peleteiro, Celia Álvarez-Bueno, Enrique G Artero, Miriam Garrido-Miguel, Vicente Martinez-Vizcaíno
BACKGROUND: Physical activity is widely perceived to be beneficial for preventing type 2 diabetes mellitus and for controlling glycaemic levels in patients with type 2 diabetes, but evidence supporting a positive effect in the control of glycaemic levels in healthy people is rather weak. The aim of this review was to estimate the effect of physical activity on glycaemic control measured by glycosylated haemoglobin (HbA 1c ) levels in non-diabetic populations, and to determine which type of physical activity has a greater influence on glycaemic control...
February 16, 2018: Sports Medicine
https://www.readbyqxmd.com/read/29453528/longitudinal-analysis-of-racial-ethnic-trends-in-quality-outcomes-in-community-health-centers-2009-2014
#13
Megan B Cole, Brad Wright, Ira B Wilson, Omar Galárraga, Amal N Trivedi
BACKGROUND: To monitor progress towards eliminating health disparities, community health centers have reported on hypertension control, diabetes control, and birthweight by race and ethnicity since 2008. OBJECTIVE: To evaluate racial/ethnic time trends in quality outcomes in health centers and to assess both within- and between-center disparities in outcomes. DESIGN AND SAMPLE: Using 2009-2014 data from all US health centers (n = 1047 centers, serving 19...
February 16, 2018: Journal of General Internal Medicine
https://www.readbyqxmd.com/read/29453449/functional-analysis-of-slc39a8-mutations-and-their-implications-for-manganese-deficiency-and-mitochondrial-disorders
#14
Eun-Kyung Choi, Trang-Tiffany Nguyen, Neil Gupta, Shigeki Iwase, Young Ah Seo
SLC39A8 encodes ZIP8, a divalent metal ion transporter. Mutations in the SLC39A8 gene are associated with congenital disorder of glycosylation type II and Leigh syndrome. Notably, affected patients with both disorders exhibited severe manganese (Mn) deficiency. The cellular function of human SLC39A8 (hSLC39A8) and the mechanisms by which mutations in this protein lead to human diseases are unclear. Herein, we show that hSLC39A8 mediates 54 Mn uptake by the cells, and its expression is regulated by Mn. While expression of wild-type hSLC39A8 increased 54 Mn uptake activity, disease-associated mutations abrogated the ability of the transporter to mediate Mn uptake into the cells, thereby providing a causal link to severe Mn deficiency...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453311/visualization-of-ligand-induced-transmembrane-signaling-in-the-full-length-human-insulin-receptor
#15
Theresia Gutmann, Kelly H Kim, Michal Grzybek, Thomas Walz, Ünal Coskun
Insulin receptor (IR) signaling plays a critical role in the regulation of metabolism and growth in multicellular organisms. IRs are unique among receptor tyrosine kinases in that they exist exclusively as covalent (αβ) 2 homodimers at the cell surface. Transmembrane signaling by the IR can therefore not be based on ligand-induced dimerization as such but must involve structural changes within the existing receptor dimer. In this study, using glycosylated full-length human IR reconstituted into lipid nanodiscs, we show by single-particle electron microscopy that insulin binding to the dimeric receptor converts its ectodomain from an inverted U-shaped conformation to a T-shaped conformation...
February 16, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29452367/variant-in-human-pofut1-reduces-enzymatic-activity-and-likely-causes-a-recessive-microcephaly-global-developmental-delay-with-cardiac-and-vascular-features
#16
Hideyuki Takeuchi, Derek Wong, Michael Schneider, Hudson H Freeze, Megumi Takeuchi, Steven J Berardinelli, Atsuko Ito, Hane Lee, Stanley F Nelson, Robert S Haltiwanger
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood...
February 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29451981/high-performance-anion-exchange-and-hydrophilic-interaction-liquid-chromatography-approaches-for-comprehensive-mass-spectrometry-based-characterization-of-the-n-glycome-of-a-recombinant-human-erythropoietin
#17
Zoltan Szabo, James R Thayer, Dietmar Reusch, Yury Agroskin, Rosa Viner, Jeff Rohrer, Sachin P Patil, Michael Krawitzky, Andreas Huhmer, Nebojsa Avdalovic, Shaheer H Khan, Yan Liu, Christopher Pohl
Comprehensive characterization of the N-glycome of a therapeutic is challenging because glycans may harbor numerous modifications (e.g. phosphorylation, sulfation, sialic acids with possible O-acetylation). The current report presents a comparison of two chromatographic platforms for the comprehensive characterization of a recombinant human erythropoietin (rhEPO) N-glycome. The two platforms include a common workflow based on 2-AB-derivatization and hydrophilic interaction chromatography (HILIC) and a native N-linked glycan workflow employing high performance anion exchange (HPAE) chromatography...
February 16, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29451141/associations-between-body-composition-indices-and-metabolic-disorders-in-chinese-adults-a-cross-sectional-observational-study
#18
Rong Zhang, Sheng-Yong Dong, Fei Wang, Cong Ma, Xiao-Lan Zhao, Qiang Zeng, Ao Fei
Background: Obesity induces dyslipidemia, hypertension, glucose intolerance, and inflammatory state, which results in atherogenic processes, diabetes, and cardiovascular disease. We usually use body composition indices, such as body mass index (BMI), body fat percentage (BFP), waist circumference-height ratio (WHtR), and waist-hip ratio (WHR) to reflect the obesity. The aim of this large population-based cross-sectional study was to investigate the associations between body composition indices and metabolic parameters in Chinese adults...
February 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29450673/recent-advances-in-enhanced-enzyme-activity-thermostability-and-secretion-by-n-glycosylation-regulation-in-yeast
#19
REVIEW
Fei Ge, Longbao Zhu, Anna Aang, Ping Song, Wanzhen Li, Yugui Tao, Guocheng Du
Yeast has been increasingly used as a host for the expression of enzymes. Compared to other expression systems, the yeast expression system has many advantages including its suitability for large-scale fermentation and its ability to modify enzymes. When expressed in yeast, many recombinant enzymes are N-glycosylated, and this may play an important role in their activity, thermostability and secretion. Although the mechanism underlying this process is not clear, the regulation of N-glycosylation by introducing or eliminating N-glycosylation at specific sites has developed into an important strategy for improving the production or catalytic properties of recombinant enzymes...
February 15, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29449376/structural-basis-for-the-glycosyltransferase-activity-of-the-salmonella-effector-ssek3
#20
Diego Esposito, Regina A Günster, Luigi Martino, Kamel El Omari, Armin Wagner, Teresa L M Thurston, Katrin Rittinger
The Salmonella secreted effector SseK3 translocates into host cells, targeting innate immune responses including NF-κB activation. SseK3 is a glycosyltransferase that transfers an N-acetylglucosamine (GlcNAc) moiety onto the guanidino group of a target arginine, modulating host cell function. However, a lack of structural information has precluded elucidation of the molecular mechanisms in arginine and GlcNAc selection. We report here the crystal structure of SseK3 in its apo form and in complex with hydrolysed UDP-GlcNAc...
February 15, 2018: Journal of Biological Chemistry
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