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Xiaoyang Guan, Patrick K Chaffey, Huan Chen, Wei Feng, Xiuli Wei, Liu-Meng Yang, Yuan Ruan, Xinfeng Wang, Yaohao Li, Kimberly B Barosh, Amy H Tran, Jaimie Zhu, Wei Liang, Yong-Tang Zheng, Xu Wang, Zhongping Tan
Many human proteins have the potential to be developed as therapeutic agents. However, side-effects caused by direct administration of natural proteins have significantly slowed expansion of protein therapeutics into the clinic. Post-translational modifications (PTMs) can improve protein properties. But due to significant knowledge gaps, we are considerably limited in our ability to apply PTMs to generate better protein therapeutics. Here, we seek to fill the gaps by studying the PTMs of a small representative chemotactic cytokine, RANTES...
December 4, 2017: Biochemistry
Fangyu Wang, Zhiqiang Lu, Xue Wang, Youcai Zhang
Bile acids (BAs) circulate between the liver and intestine, and regulate the homeostasis of glucose, lipid, and energy. Recent studies demonstrated an essential role of BAs in neurological diseases, suggesting an interaction between BAs and the nervous system. In the present study, we showed that impaired vagus function in rats induced by vagotomy resulted in an increase in bile flow without causing liver injury. The concentrations of unconjugated and glycine-conjugated BAs were increased in both serum and bile of rats after vagotomy, which was due to impaired tight junctions and thus increased passive absorption of BAs in the intestine...
November 30, 2017: Biochemical and Biophysical Research Communications
Carla Marusic, Claudio Pioli, Szymon Stelter, Flavia Novelli, Chiara Lonoce, Elena Morrocchi, Eugenio Benvenuto, Anna Maria Salzano, Andrea Scaloni, Marcello Donini
Anti-CD20 recombinant antibodies are among the most promising therapeutics for the treatment of B-cell malignancies such as non-Hodgkin lymphomas. We recently demonstrated that an immunocytokine (2B8-Fc-hIL2), obtained by fusing an anti-CD20 scFv-Fc antibody derived from C2B8 mAb (rituximab) to the human interleukin 2 (hIL-2), can be efficiently produced in Nicotiana benthamiana plants. The purified immunocytokine (IC) bearing a typical plant protein N-glycosylation profile showed a CD20 binding activity comparable to that of rituximab and was efficient in eliciting antibody-dependent cell-mediated cytotoxicity (ADCC) of human PBMC against Daudi cells, indicating its fuctional integrity...
November 27, 2017: Biotechnology and Bioengineering
Bo Zhao, Wen-Wei Gao, Ya-Jing Liu, Meng Jiang, Lian Liu, Quan Yuan, Jia-Bao Hou, Zhong-Yuan Xia
Myocardial ischemia/reperfusion injury can lead to severe brain injury. Glycogen synthase kinase 3 beta is known to be involved in myo-cardial ischemia/reperfusion injury and diabetes mellitus. However, the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear. In this study, we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats. Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin...
October 2017: Neural Regeneration Research
Mariano Malamud, Paula Carasi, Teresa Freire, María de Los Angeles Serradell
The S-layer is a (glyco)-proteinaceous envelope constituted by self-assembled subunits that form a two-dimensional lattice covering the surface of different species of Bacteria and Archaea. It could be considered as one of the most abundant biopolymers in our planet. Because of their unique self-assembly features, exhibiting repetitive identical physicochemical properties down to the subnanometer scale, as well as their involvement in specific interactions with host cells, the S-layer proteins (SLPs) show a high potential application in different areas of biotechnology, including the development of antigen carriers or new adjuvants...
November 20, 2017: Biochemical and Biophysical Research Communications
Víctor Jesús Somovilla, Iris Alicia Bermejo, Inês S Albuquerque, Nuria Martínez-Sáez, Jorge Castro-López, Fayna Garcia Martin, Ismael Compañón, Hiroshi Hinou, Shin-Ichiro Nishimura, Jesús Jiménez-Barbero, Juan Luis Asensio, Alberto Avenoza, Jesús H Busto, Ramon Hurtado-Guerrero, Jesús M Peregrina, Gonçalo J L Bernardes, Francisco Corzana
A structure-based design of a new generation tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-L-proline or 4,4-difluoroproline, at the most immunogenic domain. Binding assays using bio-layer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/π interactions...
November 22, 2017: Journal of the American Chemical Society
Xuting Zheng, Andrew D Berti, Sue McCrone, Melanie Roch, Adriana E Rosato, Warren E Rose, Baiyi Chen
Invasive methicillin-resistant Staphylococcus aureus (MRSA) treated with vancomycin (VAN) is associated with reduced VAN susceptibility and treatment failure. VAN combination therapy is one strategy to improve response, but comprehensive assessments of combinations to prevent resistance are limited. This study identifies optimal combinations to prevent the emergence of VAN-intermediate Staphylococcus aureus (VISA). Two standard MRSA and two heterogeneous VISA (hVISA) strains were exposed for 28 days in vitro to VAN alone, VAN with cefazolin (CFZ), fosfomycin (FOF), gentamicin (GEN), meropenem (MEM), rifampin (RIF), piperacillin-tazobactam (TZP) or trimethoprim-sulfamethoxazole (SXT)...
November 20, 2017: Antimicrobial Agents and Chemotherapy
Eman M Moenes, Medhat A Al-Ghobashy, Abeer A Mohamed, Maissa Y Salem
Darbepoetin alfa (DA); hyper-glycosylated Erythropoietin alfa (EPO) is an essential treatment of anemia in patients with chronic kidney failure and cancer. In this study, DA and EPO were subjected to physicochemical stress factors that might be encountered during production, transport and storage (pH, temperature, agitation, repeated freeze-thaw and oxidation). An orthogonal stability-indicating assay protocol comprised of SE-HPLC, RP-HPLC, ELISA and SDS-PAGE was developed and validated to investigate the effect of further glycosylation of DA on the pattern and kinetics of degradation...
November 4, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Michel Degueldre, Julien Echterbille, Nicolas Smargiasso, Christian Damblon, Charlotte Gouin, Gilles Mourier, Nicolas Gilles, Edwin De Pauw, Loïc Quinton
Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA), the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors...
November 18, 2017: International Journal of Molecular Sciences
Anne Ladwig, Helene Luise Walter, Jörg Hucklenbroich, Antje Willuweit, Karl-Josef Langen, Gereon Rudolph Fink, Maria Adele Rueger, Michael Schroeter
Background: Focal cerebral ischemia induces distinct neuroinflammatory processes. We recently reported the extracellular phosphor-glyco-protein osteopontin (OPN) to directly affect primary microglia in vitro, promoting survival while shifting their inflammatory profile towards a more neutral phenotype. We here assessed the effects of OPN on microglia after stroke in vivo, with focus on infarct demarcation. Methods: Animals underwent focal photothrombotic stroke and were injected intracerebroventricularly with 500 μg OPN or vehicle...
2017: Mediators of Inflammation
Bhagya N, Chandrashekar K R
Tetrandrine has been known in the treatment of tuberculosis, hyperglycemia, negative ionotropic and chronotropic effects on myocardium, malaria, cancer and fever since years together. It has been known that, tetrandrine could modulate multiple signaling molecules such as kinases of cell cycle and rat sarcoma (RAS) pathway along with proteins of tumor suppressor genes, autophagy related, β-catenins, caspases, and death receptors. Moreover, tetrandrine exhibited reversal of drug resistance by modulating P-glyco protein (P-gp) expression levels in different cancers which is an added advantage of this compound compared to other chemotherapy drugs...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Min Ma, Xinyuan Zhao, Shuo Chen, Yingyi Zhao, Lu Yang, Yu Feng, Weijie Qin, Lingjun Li, Chenxi Jia
Reversible methylation of proteins regulates the majority of cellular processes, including signal transduction, mRNA splicing, transcriptional control, DNA repair, and protein translocation. A fundamental understanding of these biological processes at the molecular level requires comprehensive characterization of the methylated proteins. Methylation is often substoichiometric, and only a very limited number of methylated proteins and sites have been confidently identified to date. Although the intrinsically basic/hydrophilic methylated peptides can be enriched by the hydrophilic interaction liquid chromatography (HILIC), other hydrophilic peptides can co-elute during the enrichment process and suppress the detection of methylated peptides...
November 1, 2017: Analytical Chemistry
Alba Di Pardo, Vittorio Maglione
No abstract text is available yet for this article.
September 2017: Neural Regeneration Research
Sivakoti Sangabathuni, Raghavendra Vasudeva Murthy, Madhuri Gade, Harikrishna Bavireddi, Suraj Toraskar, Mahesh V Sonar, Krishna N Ganesh, Raghavendra Kikkeri
The constructs and study of combinatorial libraries of structurally defined homologs extracellular matrix (ECM) glycopeptides can significantly accelerate the identification of cell surface markers involved in a variety of physiological and pathological processes. Herein, we present a simple and reliable host-guest approach to design high-throughput glyco-collagen library to modulate the primary and secondary cell lines migration process. 4-Amidoadamantyl-substituted collagen peptides and β-cyclodextrin (β-CD) appended with mono or disaccharides were used to construct self-assembled glyco-collagen conjugates (GCC) which were found to be thermally stable, with a triple helix structures and nanoneedles-like morphologies that altered cell migration processes...
October 27, 2017: ACS Nano
Christian Kellner, Anna Otte, Elisa Cappuzzello, Katja Klausz, Matthias Peipp
In the last two decades, monoclonal antibodies have revolutionized the therapy of cancer patients. Although antibody therapy has continuously been improved, still a significant number of patients do not benefit from antibody therapy. Therefore, rational optimization of the antibody molecule by Fc engineering represents a major area of translational research to further improve this potent therapeutic option. Monoclonal antibodies are able to trigger a variety of effector mechanisms. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in antibody therapy of cancer...
September 2017: Transfusion Medicine and Hemotherapy
Tim Wirt, Sophia Rosskopf, Thies Rösner, Klara Marie Eichholz, Anne Kahrs, Sebastian Lutz, Anna Kretschmer, Thomas Valerius, Katja Klausz, Anna Otte, Martin Gramatzki, Matthias Peipp, Christian Kellner
BACKGROUND: Engineering of the antibody's fragment crystallizable (Fc) by modifying the amino acid sequence (Fc protein engineering) or the glycosylation pattern (Fc glyco-engineering) allows enhancing effector functions of tumor targeting antibodies. Here, we investigated whether complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) of CD20 antibodies could be improved simultaneously by combining Fc protein engineering and glyco-engineering technologies...
September 2017: Transfusion Medicine and Hemotherapy
Cheng-Te Hsiao, Po-Wei Wang, Hua-Chien Chang, Yen-Ying Chen, Shui-Hua Wang, Yijuang Chern, Kay-Hooi Khoo
The intrinsic nature of glycosylation, namely non-template encoded, stepwise elongation and termination with a diverse range of isomeric glyco-epitopes (glycotopes), translates into ambiguity in most cases of mass spectrometry (MS)-based glycomic mapping. It is arguable that whether one needs to delineate every single glycomic entity, which may be counterproductive. Instead, one should focus on identifying as many structural features as possible that would collectively define the glycomic characteristics of a cell or tissue, and how these may change in response to self-programmed development, immuno-activation, and malignant transformation...
October 24, 2017: Molecular & Cellular Proteomics: MCP
Victor Bandlow, Susanne Liese, Daniel Lauster, Kai Ludwig, Roland R Netz, Andreas Herrmann, Oliver Seitz
Attachment of the Influenza A virus onto host cells involves multivalent interactions between virus surface hemagglutinin (HA) and sialoside-containing glyco ligands. Despite the development of extremely powerful multivalent binders of the Influenza virus and other viruses, comparably little is known about the optimal spacing of HA ligands, which ought to bridge binding sites within or across the trimeric HA molecules. To explore the criteria for ligand economical high affinity binding, we systematically probed distance-affinity relationships by means of two differently behaving scaffold types based on (i) flexible polyethylene glycol (PEG) conjugates and (ii) rigid self-assembled DNA·PNA complexes...
November 15, 2017: Journal of the American Chemical Society
Ying Liu, Ding-Kun Ji, Lei Dong, Nicolas Galanos, Yi Zang, Jia Li, Sébastien Vidal, Xiao-Peng He
Supramolecular self-assembly between perylenediimide-based glycoclusters and a red-emitting fluorophore produces structurally uniform and stable glyco-dots amenable to targeted fluorogenic imaging of liver and triple-negative breast cancer cells.
October 19, 2017: Chemical Communications: Chem Comm
(no author information available yet)
No abstract text is available yet for this article.
November 1, 2017: Glycobiology
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