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https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#1
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28106768/lipid-and-glycolipid-isomer-analyses-using-ultra-high-resolution-ion-mobility-spectrometry-separations
#2
Roza Wojcik, Ian K Webb, Liulin Deng, Sandilya V B Garimella, Spencer A Prost, Yehia M Ibrahim, Erin S Baker, Richard D Smith
Understanding the biological roles and mechanisms of lipids and glycolipids is challenging due to the vast number of possible isomers that may exist. Mass spectrometry (MS) measurements are currently the dominant approach for studying and providing detailed information on lipid and glycolipid presence and changes. However, difficulties in distinguishing the many structural isomers, due to the distinct lipid acyl chain positions, double bond locations or specific glycan types, inhibit the delineation and assignment of their biological roles...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106177/construction-and-characterisation-of-a-heparan-sulphate-heptasaccharide-microarray
#3
Jianhong Yang, Po-Hung Hsieh, Xinyue Liu, Wen Zhou, Xing Zhang, Jing Zhao, Yongmei Xu, Fuming Zhang, Robert J Linhardt, Jian Liu
A targeted heptasaccharide library was synthesised to prepare a heparan sulphate (HS) microarray. The array was probed with two glycan-binding proteins, HS 3-O-sulphotransferase 1 and antithrombin, demonstrating the binding selectivity between HS and proteins. The HS microarray technique will accelerate the understanding of the structure and function relationships of HS.
January 20, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28106125/baba-dependent-binding-of-helicobacter-pylori-to-human-gastric-mucins-cause-aggregation-that-inhibits-proliferation-and-is-regulated-via-arss
#4
Emma C Skoog, Médea Padra, Anna Åberg, Pär Gideonsson, Ikenna Obi, Macarena P Quintana-Hayashi, Anna Arnqvist, Sara K Lindén
Mucins in the gastric mucus layer carry a range of glycan structures, which vary between individuals, can have antimicrobial effect or act as ligands for Helicobacter pylori. Mucins from various individuals and disease states modulate H. pylori proliferation and adhesin gene expression differently. Here we investigate the relationship between adhesin mediated binding, aggregation, proliferation and adhesin gene expression using human gastric mucins and synthetic adhesin ligand conjugates. By combining measurements of optical density, bacterial metabolic activity and live/dead stains, we could distinguish bacterial aggregation from viability changes, enabling elucidation of mechanisms behind the anti-prolific effects that mucins can have...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28104756/sugar-nucleotide-quantification-by-liquid-chromatography-tandem-mass-spectrometry-reveals-a-distinct-profile-in-plasmodium-falciparum-sexual-stage-parasites
#5
Borja López-Gutiérrez, Rhoel R Dinglasan, Luis Izquierdo
The obligate intracellular lifestyle of Plasmodium falciparum and the difficulties to obtain sufficient amounts of biological material has hampered the study of specific metabolic pathways in the malaria parasite. Thus, for example, the pools of sugar nucleotides required to fuel glycosylation reactions have never been studied in-depth in well-synchronized asexual parasites or in other stages of its life cycle. These metabolites are of critical importance, especially considering the renewed interest in the presence of N -, O - and other glycans in key parasite proteins...
January 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28104755/n-glycosylation-of-human-sphingomyelin-phosphodiesterase-acid-like-3a-smpdl3a-is-essential-for-stability-secretion-and-activity
#6
Mathew Traini, Raani Kumaran, Morten Thaysen-Andersen, Maaike Kockx, Wendy Jessup, Leonard Kritharides
Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a recently identified phosphodiesterase, which is a secreted N -linked glycoprotein. SMPDL3A is highly homologous to acid sphingomyelinase (aSMase), but unlike aSMase can not cleave sphingomyelin. Rather, SMPDL3A hydrolyzes nucleotide tri- and diphosphates and their derivatives. While recent structural studies have shed light on these unexpected substrate preferences, many other aspects of SMPDL3A biology which may give insight into its function in vivo remain obscure...
January 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28103685/an-effective-bacterial-fucosidase-for-glycoprotein-remodeling
#7
Tsung-I Tsai, Shiou-Ting Li, Chiu-Ping Liu, Karen Y Chen, Sachin S Shivatare, Chin-Wei Lin, Shih-Fen Liao, Chih-Wei Lin, Tsui-Ling Hsu, Ying-Ta Wu, Ming-Hung Tsai, Meng-Yu Lai, Nan-Horng Lin, Chung-Yi Wu, Chi-Huey Wong
Fucose is an important component of many oligo- and polysaccharide structures as well as glycoproteins and glycolipids, which are often associated with a variety of physiological processes ranging from fertilization, embryogenesis, signal transduction, and disease progression, such as rheumatoid arthritis, inflammation, and cancer. The enzyme α-l-fucosidase is involved in the cleavage of the fucosidic bond in glycans and glycoconjugates, particularly the Fuc-α-1,2-Gal, Fuc-α-1,3/4-GlcNAc, and Fuc-α-1,6-GlcNAc linkages...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28102671/structural-analysis-of-glycosylated-intact-hiv-1-gp120-b12-antibody-complex-using-hydroxyl-radical-protein-footprinting
#8
Xiaoyan Li, Oliver C Grant, Keigo Ito, Aaron Wallace, Shixia Wang, Peng Zhao, Lance Wells, Shan Lu, Robert J Woods, Joshua S Sharp
Glycoprotein gp120 is a surface antigen and virulence factor of the human immunodeficiency virus-1 (HIV-1). Broadly neutralizing antibodies (bNAbs) that are reactive to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system due to its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions...
January 19, 2017: Biochemistry
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
#9
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/28101612/abolishment-of-n-glycan-mannosylphosphorylation-in-glyco-engineered-saccharomyces-cerevisiae-by-double-disruption-of-mnn4-and-mnn14-genes
#10
Yeong Hun Kim, Ji-Yeon Kang, Jin Young Gil, Sang-Yoon Kim, Keun Koo Shin, Hyun Ah Kang, Jeong-Yoon Kim, Ohsuk Kwon, Doo-Byoung Oh
Mannosylphosphorylated glycans are found only in fungi, including yeast, and the elimination of mannosylphosphates from glycans is a prerequisite for yeast glyco-engineering to produce human-compatible glycoproteins. In Saccharomyces cerevisiae, MNN4 and MNN6 genes are known to play roles in mannosylphosphorylation, but disruption of these genes does not completely remove the mannosylphosphates in N-glycans. This study was performed to find unknown key gene(s) involved in N-glycan mannosylphosphorylation in S...
January 18, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28100988/simultaneous-analyses-of-n-linked-and-o-linked-glycans-of-ovarian-cancer-cells-using-solid-phase-chemoenzymatic-method
#11
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/28100831/coexistence-of-potent-hiv-1-broadly-neutralizing-antibodies-and-antibody-sensitive-viruses-in-a-viremic-controller
#12
Natalia T Freund, Haoqing Wang, Louise Scharf, Lilian Nogueira, Joshua A Horwitz, Yotam Bar-On, Jovana Golijanin, Stuart A Sievers, Devin Sok, Hui Cai, Julio C Cesar Lorenzi, Ariel Halper-Stromberg, Ildiko Toth, Alicja Piechocka-Trocha, Harry B Gristick, Marit J van Gils, Rogier W Sanders, Lai-Xi Wang, Michael S Seaman, Dennis R Burton, Anna Gazumyan, Bruce D Walker, Anthony P West, Pamela J Bjorkman, Michel C Nussenzweig
Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice or macaques can treat or prevent infection. However, bNAbs typically fail to neutralize coexisting autologous viruses due to antibody-mediated selection against sensitive viral strains. We describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. Neutralization was attributed to three different bNAbs targeting nonoverlapping sites on the HIV-1 envelope trimer (Env)...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100567/mecp2-regulated-glycogenes-contribute-to-proliferation-and-apoptosis-of-gastric-cancer-cells
#13
Yannan Qin, Lingyu Zhao, Xiaofei Wang, Dongdong Tong, Christopher Hoover, Fei Wu, Yingxun Liu, Lumin Wang, Liying Liu, Lei Ni, Tusheng Song, Chen Huang
Aberrant glycogene and glycan expression is intimately associated with carcinogenesis, invasion, and metastasis of gastric cancer (GC); however the regulatory mechanisms for glycogenes in GC cells remain unclear. Methyl-CpG-binding protein 2 (MeCP2) regulates genes by binding to methylated promoters, and in our previous work we found that it is overexpressed in GC cell lines and tissues, functioning as an oncogene. In this study we detected the expression of 212 glycogenes in MeCP2 silenced GC cells versus control using the Agilent Whole Human Genome Microarray and mining the data through bioinformatic analysis...
January 18, 2017: Glycobiology
https://www.readbyqxmd.com/read/28097795/impaired-n-linked-glycosylation-of-uptake-and-efflux-transporters-in-human-nonalcoholic-fatty-liver-disease
#14
John D Clarke, Petr Novak, April D Lake, Rhiannon N Hardwick, Nathan J Cherrington
BACKGROUND & AIMS: N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression...
January 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28096352/recognition-of-protein-linked-glycans-as-a-determinant-of-peptidase-activity
#15
Ilit Noach, Elizabeth Ficko-Blean, Benjamin Pluvinage, Christopher Stuart, Meredith L Jenkins, Denis Brochu, Nakita Buenbrazo, Warren Wakarchuk, John E Burke, Michel Gilbert, Alisdair B Boraston
The vast majority of proteins are posttranslationally altered, with the addition of covalently linked sugars (glycosylation) being one of the most abundant modifications. However, despite the hydrolysis of protein peptide bonds by peptidases being a process essential to all life on Earth, the fundamental details of how peptidases accommodate posttranslational modifications, including glycosylation, has not been addressed. Through biochemical analyses and X-ray crystallographic structures we show that to hydrolyze their substrates, three structurally related metallopeptidases require the specific recognition of O-linked glycan modifications via carbohydrate-specific subsites immediately adjacent to their peptidase catalytic machinery...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095317/formulation-of-liposomes-functionalized-with-lotus-lectin-and-effective-in-targeting-highly-proliferative-cells
#16
Cinzia Della Giovampaola, Antonietta Capone, Leonardo Ermini, Pietro Lupetti, Elisa Vannuccini, Federica Finetti, Sandra Donnini, Marina Ziche, Agnese Magnani, Gemma Leone, Claudio Rossi, Floriana Rosati, Claudia Bonechi
BACKGROUND: Liposomes, used to improve the therapeutic index of new and established drugs, have advanced with the insertion of active targeting. The lectin from Lotus tetragonolobus (LTL), which binds glycans containing alpha-1,2-linked fucose, reveals surface regionalized glycoepitopes in highly proliferative cells not detectable in normally growing cells. In contrast, other lectins localize the corresponding glycoepitopes all over the cell surface. LTL also proved able to penetrate the cells by an unconventional uptake mechanism...
January 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28093470/active-site-maturation-and-activity-of-the-copper-radical-oxidase-glxa-is-governed-by-a-tryptophan-residue
#17
Amanda K Chaplin, Dimitri A Svistunenko, Michael Hough, Michael T Wilson, Erik Vijgenboom, Jonathan Ar Worrall
GlxA from Streptomyces lividans is a mononuclear copper-radical oxidase and a member of the auxiliary activity family 5 (AA5). Its domain organisation and low sequence homology make it a distinct member of the AA5 family in which the fungal galactose 6-oxidase (Gox) is the best-characterized. GlxA is a key cuproenzyme in the copper-dependent morphological development of S. lividans with a function that is linked to the processing of an extracytoplasmic glycan. The catalytic site in GlxA and Gox contain two distinct one-electron acceptors comprising the copper ion and a 3'-(S-cysteinyl) tyrosine...
January 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28093404/development-and-application-of-an-algorithm-to-compute-weighted-multiple-glycan-alignments
#18
Masae Hosoda, Yukie Akune, Kiyoko F Aoki-Kinoshita
MOTIVATION: A glycan consists of monosaccharides linked by glycosidic bonds, has branches and forms complex molecular structures. Databases have been developed to store large amounts of glycan-binding experiments, including glycan arrays with glycan binding proteins (GBPs). However, there are few bioinformatics techniques to analyze large amounts of data for glycans because there are few tools that can handle the complexity of glycan structures. Thus, we have developed the MCAW (Multiple Carbohydrate Alignment with Weights) tool that can align multiple glycan structures, to aid in the understanding of their function as binding recognition molecules...
January 16, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28092665/antibody-10-1074-suppresses-viremia-in-hiv-1-infected-individuals
#19
Marina Caskey, Till Schoofs, Henning Gruell, Allison Settler, Theodora Karagounis, Edward F Kreider, Ben Murrell, Nico Pfeifer, Lilian Nogueira, Thiago Y Oliveira, Gerald H Learn, Yehuda Z Cohen, Clara Lehmann, Daniel Gillor, Irina Shimeliovich, Cecilia Unson-O'Brien, Daniela Weiland, Alexander Robles, Tim Kümmerle, Christoph Wyen, Rebeka Levin, Maggi Witmer-Pack, Kemal Eren, Caroline Ignacio, Szilard Kiss, Anthony P West, Hugo Mouquet, Barry S Zingman, Roy M Gulick, Tibor Keler, Pamela J Bjorkman, Michael S Seaman, Beatrice H Hahn, Gerd Fätkenheuer, Sarah J Schlesinger, Michel C Nussenzweig, Florian Klein
Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074...
January 16, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28092124/active-site-mapping-of-xylan-deconstructing-enzymes-with-arabinoxylan-oligosaccharides-produced-by-automated-glycan-assembly
#20
Deborah Senf, Colin Ruprecht, Goswinus de Kruijff, Sebastian Simonetti, Frank Schuhmacher, Peter Seeberger, Fabian Pfrengle
Xylan-degrading enzymes are crucial for the deconstruction of hemicellulosic biomass, making the hydrolysis products available for various industrial applications such as biofuel production. To determine the substrate specificities of these enzymes, we prepared a collection of complex xylan oligosaccharides by automated glycan assembly. Seven differentially protected building blocks provided the basis for the modular assembly of 2-substituted, 3-substituted, and 2-/3-substituted arabino- and glucuronoxylan oligosaccharides...
January 16, 2017: Chemistry: a European Journal
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