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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/28345922/the-synthetic-access-toward-cycloastragenol-glycosides
#2
Ting Liu, Jin-Xi Liao, Yang Hu, Yuan-Hong Tu, Jian-Song Sun
The first efficient synthetic approach toward four types of the cycloartane glycosides, the cycloastragenol 25-O, 3-O, 3,6-O-bis, and 3,25-O-bisglycoside, have been established, which featured the PPY-mediated, concentration-controlled acetylation and Au(I)-catalyzed Yu glycosylation. Through the synthetic investigation, the reactivity sequence of the four OHs in cycloastragenol was fixed for the first time and a detour strategy for the highly efficient removal of bulky pivaloyl protecting groups was discovered...
March 27, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28345880/detecting-proteins-glycosylation-by-a-homogeneous-reaction-system-with-zwitterionic-gold-nanoclusters
#3
Jinan Li, Jing Liu, Zheyi Liu, Yuan Tan, Xiaoyan Liu, Fangjun Wang
Homogeneous gold nanoclusters (Au NCs) have been widely utilized in drug delivery, chemical sensing, bioassays and bio-labeling due to their unique physical and chemical properties. However, little attention has been paid to their application in detecting protein post-translational modifications. Herein, we describe development of a homogeneous reaction system with water-soluble zwitterionic Au NCs to capture glycopeptides from complex biological samples. The unique characteristics of Au NCs, such as their molecular-like properties, the excellent homogeneity in aqueous solution, the organic solvent respon-sive precipitation, and the easy preparation in only 4...
March 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28345792/adding-fast-acting-insulin-aspart-to-basal-insulin-significantly-improved-glycaemic-control-in-patients-with-type-2-diabetes-a-randomised-18-week-open-label-phase-3-trial-onset-3
#4
Helena W Rodbard, Devjit Tripathy, Maricela Vidrio Velázquez, Marek Demissie, Søren Can Tamer, Milivoj Piletič
AIM: To confirm glycaemic control superiority of mealtime fast-acting insulin aspart (faster aspart) in a basal-bolus (BB) regimen versus basal-only insulin. MATERIALS AND METHODS: In this open-label, randomised, 18-week trial (51 sites; 6 countries) adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c ] ±SD: 7.9 ± 0.7% [63.1 ± 7.5 mmol/mol) receiving basal insulin and oral antidiabetic drugs underwent 8-week optimisation of prior once-daily basal insulins followed by randomisation 1:1 to a BB regimen with faster aspart (n = 116) or continuation of once-daily basal insulin (n = 120), both with metformin...
March 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28345721/dissecting-the-structural-basis-for-the-intracellular-delivery-of-osw-1-by-fluorescent-probes
#5
M Hiraizumi, R Komatsu, T Shibata, Y Ohta, K Sakurai
The structural basis for the intracellular delivery of OSW-1 is investigated using fluorescent derivatives of OSW-1 and its closely related congeners. Despite the large differences in activity, all the fluorescent probes are found to translocate across the plasma membrane to the ER and Golgi apparatus. This observation suggests that the glycosylated cholestane moiety plays an important role in the cell internalization and intracellular localization property of OSW-1.
March 27, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28345659/oral-chromium-picolinate-impedes-hyperglycemia-induced-atherosclerosis-and-inhibits-proatherogenic-protein-tsp-1-expression-in-stz-induced-type-1-diabetic-apoe-mice
#6
Rituparna Ganguly, Soumyadip Sahu, Vahagn Ohanyan, Rebecca Haney, Ronaldo J Chavez, Shivani Shah, Siri Yalamanchili, Priya Raman
Increasing evidence suggests thrombospondin-1 (TSP-1), a potent proatherogenic matricellular protein, as a putative link between hyperglycemia and atherosclerotic complications in diabetes. We previously reported that the micronutrient chromium picolinate (CrP), with long-standing cardiovascular benefits, inhibits TSP-1 expression in glucose-stimulated human aortic smooth muscle cells in vitro. Here, we investigated the atheroprotective action of orally administered CrP in type 1 diabetic apolipoprotein E-deficient (ApoE(-/-)) mice and elucidated the role of TSP-1 in this process...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344996/codon-optimization-leads-to-functional-impairment-of-rd114-tr-envelope-glycoprotein
#7
Eleonora Zucchelli, Monika Pema, Anna Stornaiuolo, Claudia Piovan, Cinzia Scavullo, Erica Giuliani, Sergio Bossi, Stefano Corna, Claudia Asperti, Claudio Bordignon, Gian-Paolo Rizzardi, Chiara Bovolenta
Lentiviral vectors (LVs) are a highly valuable tool for gene transfer currently exploited in basic, applied, and clinical studies. Their optimization is therefore very important for the field of vectorology and gene therapy. A key molecule for LV function is the envelope because it guides cell entry. The most commonly used in transiently produced LVs is the vesicular stomatitis virus glycoprotein (VSV-G) envelope, whose continuous expression is, however, toxic for stable LV producer cells. In contrast, the feline endogenous retroviral RD114-TR envelope is suitable for stable LV manufacturing, being well tolerated by producer cells under constitutive expression...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344780/abnormal-glycosylation-in-joubert-syndrome-type-10
#8
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/28344751/management-of-critically-ill-patients-with-diabetes
#9
REVIEW
Livier Josefina Silva-Perez, Mario Alberto Benitez-Lopez, Joseph Varon, Salim Surani
Disorders of glucose homeostasis, such as stress-induced hypoglycemia and hyperglycemia, are common complications in patients in the intensive care unit. Patients with preexisting diabetes mellitus (DM) are more susceptible to hyperglycemia, as well as a higher risk from glucose overcorrection, that may results in severe hypoglycemia. In critically ill patients with DM, it is recommended to maintain a blood glucose range between 140-180 mg/dL. In neurological patients and surgical patients, tighter glycemic control (i...
March 15, 2017: World Journal of Diabetes
https://www.readbyqxmd.com/read/28343125/structural-modeling-of-human-organic-cation-transporters
#10
Tikam Chand Dakal, Rajender Kumar, Dindial Ramotar
Human organic cation transporters (hOCTs) belong to solute carriers (SLC) 22 family of membrane proteins that play a central role in transportation of chemotherapeutic drugs for several clinical and pathological conditions, including cancer and diabetes. These transporters mediate drug transport; however, the precise mechanism of drug-binding and transport by them is not fully uncovered yet, partly due to unavailability of any crystal structure record. In this work, we performed a multi-phasic approach to compute the 3D structural models of seven human organic cation transporters (hOCTs) starting from primary protein sequence...
March 18, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28342833/a-high-density-cho-s-transient-transfection-system-comparison-of-expicho-and-expi293
#11
Nina K Jain, Susan Barkowski-Clark, Richard Altman, Krista Johnson, Fang Sun, Jonathan Zmuda, Chao Yan Liu, Adriana Kita, Ryan Schulz, Alyssa Neill, Robert Ballinger, Rekha Patel, Jian Liu, Alinafe Mpanda, Brian Huta, Henry Chiou, Walter Voegtli, Tadas Panavas
Chinese Hamster Ovary (CHO) cells are the principal mammalian host used for stable cell line generation and biotherapeutic protein production. Until recently, production of milligrams to grams of protein in CHO transient systems was challenging. As such, Human Embryonic Kidney (HEK293) cells are the most common mammalian cell type used for transient transfection. The post-translational modifications (PTMs) of a protein are dictated in part by the cell line used for expression, and changes in PTMs have been shown to affect both the activity and biophysical properties of proteins...
March 22, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28342150/expression-and-characterization-of-human-%C3%AE-1-4-galactosyltransferase-1-%C3%AE-4galt1-using-silkworm-baculovirus-expression-system
#12
Daisuke Morokuma, Jian Xu, Masato Hino, Hiroaki Mon, Jasmeen S Merzaban, Masateru Takahashi, Takahiro Kusakabe, Jae Man Lee
Baculovirus expression vector system (BEVS) is widely known as a mass-production tool to produce functional recombinant glycoproteins except that it may not be always suitable for medical practice due to the differences in the structure of N-linked glycans between insects and mammalian. Currently, various approaches have been reported to alter N-linked glycan structures of glycoproteins derived from insects into terminally sialylated complex-type N-glycans. In the light of those studies, we also proposed in vitro maturation of N-glycan with mass-produced and purified glycosyltransferases by silkworm-BEVS...
March 24, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28341406/sweet-new-roles-for-protein-glycosylation-in-prokaryotes
#13
REVIEW
Jerry Eichler, Michael Koomey
Long-held to be a post-translational modification unique to Eukarya, it is now clear that both Bacteria and Archaea also perform protein glycosylation, namely the covalent attachment of mono- to polysaccharides to specific protein targets. At the same time, many of the roles assigned to this protein-processing event in eukaryotes, such as guiding protein folding/quality control, intracellular trafficking, dictating cellular recognition events and others, do not apply or are even irrelevant to prokaryotes. As such, protein glycosylation must serve novel functions in Bacteria and Archaea...
March 21, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28338992/identification-of-the-eucalyptus-grandis-chitinase-gene-family-and-expression-characterization-under-different-biotic-stress-challenges
#14
Peri A Tobias, Nanette Christie, Sanushka Naidoo, David I Guest, Carsten Külheim
Eucalyptus grandis (W. Hill ex Maiden) is an Australian Myrtaceae tree grown for timber in many parts of the world and for which the annotated genome sequence is available. Known to be susceptible to a number of pests and diseases, E. grandis is a useful study organism for investigating defense responses in woody plants. Chitinases are widespread in plants and cleave glycosidic bonds of chitin, the major structural component of fungal cell walls and arthropod exoskeletons. They are encoded by an important class of genes known to be up-regulated in plants in response to pathogens...
March 13, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28338946/instrumental-variable-methods-for-continuous-outcomes-that-accommodate-nonignorable-missing-baseline-values
#15
Ashkan Ertefaie, James H Flory, Sean Hennessy, Dylan S Small
Instrumental variable (IV) methods provide unbiased treatment effect estimation in the presence of unmeasured confounders under certain assumptions. To provide valid estimates of treatment effect, treatment effect confounders that are associated with the IV (IV-confounders) must be included in the analysis, and not including observations with missing values may lead to bias. Missing covariate data are particularly problematic when the probability that a value is missing is related to the value itself, which is known as nonignorable missingness...
March 16, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28338695/unprecedented-highly-efficient-capture-of-glycopeptides-by-fe3o4-mg-mof-74-core-shell-nanoparticles
#16
Jie Li, Jiaxi Wang, Yun Ling, Zhenxia Chen, Mingxia Gao, Xiangmin Zhang, Yaming Zhou
Magnetic Fe3O4 nanospheres coated with Mg-MOF-74 have been facilely prepared via epitaxial growth. Owing to the intrinsic hydrophilic pore surface and size-exclusive properties of Mg-MOF-74, the Fe3O4@Mg-MOF-74 core-shell nanoparticles show effective and selective enrichment of 441 N-glycosylation sites of 418 glycopeptides from 125 glycoproteins in 1 μL of human serum.
March 24, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28337877/correlation-between-cystatin-c-and-retinopathy-of-type-two-diabetes-mellitus-patients
#17
C Qian, G M Wan, P S Yan, W Z Wang, S Z Liang, Y Dong
Diabetic retinopathy is one of most common diabetic microvascular complications. In recent years the incidence of the disease has increased, hence early diagnosis and treatment are of great importance. In order to find reliable biological indexes to diagnose and treat type-two diabetes mellitus promptly, this study focused on the correlation between Cystatin C (Cys C) and retinopathy of type-two diabetes mellitus patients. One hundred and eighty type-two diabetes mellitus patients and one hundred healthy controls (the control group) were chosen in this study...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337749/branched-i%C3%A2-antigens-on-leukemia-cells-enhanced-sensitivity-against-natural-killer-cell-cytotoxicity-through-affecting-the-target-effector-interaction
#18
Yen-Hua Lee, Yi-Jen Liao, Chin-Han Huang, Fu-Ling Chang, Ting-Hsi Fan, Yuh-Ching Twu
BACKGROUND: The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations for promoting the tumorigenesis, metastasis, and evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, converting the straight i to branched I histo-blood group antigens, reportedly could influence the migration, invasion, and metastasis of solid tumors. STUDY DESIGN AND METHODS: We first chose the highly cytotoxic natural killer (NK)-92MI cells as effector against leukemia for this cell line has been used in several clinical trials...
March 24, 2017: Transfusion
https://www.readbyqxmd.com/read/28337402/a-brief-review-of-bioinformatics-tools-for-glycosylation-analysis-by-mass-spectrometry
#19
Pei-Lun Tsai, Sung-Fang Chen
The purpose of this review is to provide updated information regarding bioinformatic software for the use in the characterization of glycosylated structures since 2013. A comprehensive review by Woodin et al.Analyst 138: 2793-2803, 2013 (ref. 1) described two main approaches that are introduced for starting researchers in this area; analysis of released glycans and the identification of glycopeptide in enzymatic digests, respectively. Complementary to that report, this review focuses on mass spectrometry related bioinformatics tools for the characterization of N-linked and O-linked glycopeptides...
2017: Mass Spectrometry
https://www.readbyqxmd.com/read/28336960/co-expression-of-bira-with-biotin-bait-achieves-in-vivo-biotinylation-of-overexpressed-stable-n-glycosylated-srage-in-transgenic-silkworms
#20
Miyuki Kumano-Kuramochi, Ken-Ichiro Tatematsu, Mayumi Ohnishi-Kameyama, Mari Maeda-Yamamoto, Toshiro Kobori, Hideki Sezutsu, Sachiko Machida
Here, we demonstrated the expression of the N-glycosylated extracellular ligand binding domain of receptor for advanced glycation end products (sRAGE) in middle silk glands (MSGs) of transgenic silkworms using the GAL4/UAS system. Over 1 mg of sRAGE was obtained from one transgenic silkworm. sRAGE purified from the silkworm exhibited good stability and maintained specific ligand-binding ability. In addition, N-glycan analysis of sRAGE revealed that N-glucan completely lacked potentially allergenic fucose...
March 23, 2017: Scientific Reports
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