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Peptide mimics

Leila Mekkaoui, Farhaan Parekh, Ekaterini Kotsopoulou, David Darling, Glenda Dickson, Gordon W Cheung, Lucas Chan, Kirsty MacLellan-Gibson, Giada Mattiuzzo, Farzin Farzaneh, Yasuhiro Takeuchi, Martin Pule
Lentiviral vectors (LVs) have recently witnessed an increasing demand in research and clinical applications. Their current purification processes represent the main bottleneck in their widespread use, as the methods used are cumbersome and yield low recoveries. We aimed to develop a one-step method to specifically purify LVs, with high yields and reduced levels of impurities, using the biotin-streptavidin system. Herein, packaging HEK293T cells were genetically engineered with a cyclical biotin-mimicking peptide displayed on a CD8α stalk, termed cTag8...
December 14, 2018: Molecular Therapy. Methods & Clinical Development
Fany Reffuveille, Jérôme Josse, Frédéric Velard, Fabien Lamret, Jennifer Varin-Simon, Marie Dubus, Evan F Haney, Robert E W Hancock, Céline Mongaret, Sophie C Gangloff
Prosthesis and joint infections are an important threat in public health, especially due to the development of bacterial biofilms and their high resistance to antimicrobials. Biofilm-associated infections increase mortality and morbidity rates as well as hospitalization costs. Prevention is the best strategy for this serious issue, so there is an urgent need to understand the signals that could induce irreversible bacterial adhesion on a prosthesis. In this context, we investigated the influence of the bone environment on surface adhesion by a methicillin-susceptible Staphylococcus aureus strain...
2018: Frontiers in Microbiology
Yi-Ting Sun, Matthew D Shortridge, Gabriele Varani
The RRM (RNA-recognition motif), the most abundant RNA-binding motif in eukaryotes, is a small folded domain of about 90 amino acids, yet the β2-β3 hairpin corresponding to strands 2 and 3 of the β-sheet, and the intervening loop makes essential interactions with RNA in many RRM complexes. We designed a series of small cyclic peptides mimics of the β2-β3 hairpin of Rbfox2 protein, that recognize the terminal loop of precursor miR-20b, to investigate whether it is possible to mimic the full RNA-binding protein with a minimal structurally pre-organized peptide...
December 11, 2018: Chembiochem: a European Journal of Chemical Biology
H-H Sun, P-F Sun, W-Y Liu
OBJECTIVE: This study aims to investigate whether miR-98-5p can participate in the myocardial differentiation of bone marrow mesenchymal stem cells (MSCs) by regulating TBX5. MATERIALS AND METHODS: In this study, we first identified the MSCs that were isolated from rat bone marrow samples. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect mRNA expressions of cardiac-related genes, including brain natriuretic peptide (BNP), α-actinin, and Islet-1...
November 2018: European Review for Medical and Pharmacological Sciences
Cameron Fraser, Jeremy Ryan, Kristopher Sarosiek
Apoptosis (programmed cell death) is activated by a wide variety of cellular stresses or insults and is vital for proper mammalian development as well as the maintenance of organismal homeostasis. The apoptosis pathway is also engaged by many common types of anticancer therapies and ionizing radiation, which contributes to the regressions of tumors or the toxic side effects of treatment. Due to the importance of maintaining healthy cell survival or the efficient clearance of cancer cells, the BH3 profiling assay was developed to functionally measure the state of the apoptosis pathway in any given cells...
2019: Methods in Molecular Biology
Seonghoon Kim, Marcos M Pires, Wonpil Im
Peptidoglycan (PG) biosynthesis and assembly are needed for bacterial cell wall formation. Lipid II is the precursor in the PG biosynthetic pathway and carries a nascent PG unit that is processed by glycosyltransferases. Despite its immense therapeutic value as a target of several classes of antibiotics, the conformational ensemble of lipid II in bacterial membranes and its interactions with membrane-anchored enzymes remain elusive. In this work, lipid II and its elongated forms (lipid VI and lipid XII) were modeled and simulated in bilayers of POPE (palmitoyl-oleoyl-phosphatidyl-ethanolamine) and POPG (palmitoyl-oleoyl-phosphatidyl-glycerol) that mimic the prototypical composition of Gram-negative cytoplasmic membranes...
December 7, 2018: Scientific Reports
Satoshi Tsuzuki, Shinhye Lee, Yusaku Kimoto, Tatsuya Sugawara, Yuki Manabe, Kazuo Inoue
Class B scavenger receptor family members, scavenger receptor B1 (SR-B1) and cluster of differentiation 36 (CD36), are broadly expressed cell-surface proteins, both of which are believed to serve as multifaceted players in lipid and lipoprotein metabolism in mammals. Because of its presence in the apical part of taste receptor cells within circumvallate taste buds and its ability to recognise long-chain fatty acids, CD36 has been believed to participate in the sensing of the lipid species within the oral cavity...
2018: Biomedical Research
Hakim Echchannaoui, Jutta Petschenka, Edite Antunes Ferreira, Beate Hauptrock, Carina Lotz-Jenne, Ralf-Holger Voss, Matthias Theobald
Genetic engineering of T cells with a T cell receptor (TCR) targeting tumor antigen is a promising strategy for cancer immunotherapy. Inefficient expression of the introduced TCR due to TCR mispairing may limit the efficacy and adversely affect the safety of TCR gene therapy. Here, we evaluated the safety and therapeutic efficiency of an optimized single-chain TCR (scTCR) specific for an HLA-A2.1-restricted (non-mutated) p53(264-272) peptide in adoptive T cell transfer (ACT) models using our unique transgenic mice expressing human p53 and HLA-A2...
November 15, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Vilde Olsson, Lisa Joos, Shanshuo Zhu, Kris Gevaert, Melinka A Butenko, Ive De Smet
During the past decade, a flurry of research focusing on the role of peptides as short- and long-distance signaling molecules in plant cell communication has been undertaken. Here,we focus on peptides derived from nonfunctional precursors, and we address several key questions regarding peptide signaling. We provide an overview of the regulatory steps involved in producing a biologically active peptide ligand that can bind its corresponding receptor(s) and discuss how this binding and subsequent activation lead to specific cellular outputs...
December 10, 2018: Annual Review of Plant Biology
Chengwei Liu, Shicheng Shi, Yongmei Liu, Ruzhang Liu, Roger Lalancette, Roman Szostak, Michal Szostak
The synthesis, crystal structures, and reactivity of the most twisted acyclic amides described to date are reported. Substitution at the nitrogen atom in simple benzamides with Ts and acyl or carbamate groups provides a unique way to achieve almost perpendicular twist in N-acyclic amides (τ = 77°, N = Ac; τ = 87°, N = Boc). The overlap between the Nlp and CO π* orbital is disrupted due to geometrical constraints around the N-substituents. The perpendicular acyclic twisted amides represent a transition state mimic of cis-trans peptide isomerization thus far only accessible by excessively twisted bridged lactams...
December 10, 2018: Organic Letters
Anthony J Metrano, Scott J Miller
Nature's catalytic machinery has provided endless inspiration for chemists. While the enzymatic ideal has yet to be fully realized, the field has made tremendous strides toward synthetic, small-molecule catalysts for a wide array of transformations, often drawing upon biological concepts in their design. One strategy that has been particularly influenced by enzymology is peptide catalysis, wherein oligopeptides are implemented as chiral catalysts in synthetically relevant reactions. The fundamental goal has been to mimic enzymatic active sites by taking advantage of secondary structures that allow for multifunctional activation of substrates within a framework of significantly reduced molecular complexity...
December 11, 2018: Accounts of Chemical Research
Yuanjun Deng, Yang Cai, Lele Liu, Xueping Lin, Pingfan Lu, Yiyan Guo, Min Han, Gang Xu
Protein tyrosine (Tyr) nitration, the covalent addition of a nitro group (• NO2 ) to Tyr residues, is emerging as a candidate mechanism of endothelial dysfunction. Previous studies have shown that Tyr nitration is primarily induced by nitrosative stress, a process characterized by the production of reactive nitrogen species, especially peroxynitrite anion (ONOO- ), which is considered a secondary product of NO in the presence of superoxide radicals (O2 •- ). However, the impact of nitrosative stress-induced Tyr nitration on endothelial dysfunction has not been thoroughly elucidated to date...
December 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Weijian Fan, Xiang Li, Dongping Zhang, Haiying Li, Haitao Shen, Yizhi Liu, Gang Chen
Although microRNA-144-3p (miRNA-144-3p) has been shown to suppress tumor proliferation and invasion, its function in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) remains unclear. Thus, this study was designed to investigate the role of miRNA-144-3p in ICH. To accomplish this, we used adult male Sprague-Dawley rats to establish an in vivo ICH model by injecting autologous blood, while cultured primary rat cortical neurons were exposed to oxyhemoglobin (OxyHb) to mimic ICH in vitro. To examine the role of miRNA-144-3p in ICH-induced SBI, we used an miRNA-144-3p mimic and inhibitor both in vivo and in vitro...
December 4, 2018: Cell Transplantation
Asnet Mary John, Akanitt Jittmittraphap, Siriporn Chattanadee, A Alwin Prem Anand, R Shenbagarathai, Pornsawan Leaungwutiwong
Dengue fever is the most prevalent arthropod-borne viral disease, and no specific therapeutic or promising antiviral drug is available for its treatment. Peptide inhibitors are less toxic than synthetic compounds and have found proven effective against viral infections. Here, three peptides that mimic part of the E protein of the dengue virus (DENV) were synthesized and evaluated for their inhibitory activity against four serotypes of DENV in African green monkey kidney (Vero) and rhesus macaque (Macaca mulatta) monkey kidney (LLC-MK2) cell lines...
November 30, 2018: Virus Research
Cheng Jiang, Wei-Jye Lin, Benoit Labonté, Carol A Tamminga, Gustavo Turecki, Eric J Nestler, Scott J Russo, Stephen R Salton
Patients with major depressive disorder (MDD) often have structural and functional deficits in the ventromedial prefrontal cortex (vmPFC), but the underlying molecular pathways are incompletely understood. The neuropeptide precursor VGF (non-acronymic) plays a critical role in depression and antidepressant efficacy in hippocampus and nucleus accumbens, however its function in vmPFC has not been investigated. Here, we show that VGF levels were reduced in Brodmann area 25 (a portion of human vmPFC) of MDD patients and in mouse vmPFC following chronic restraint stress (CRS), and were increased by ketamine in mouse vmPFC...
November 20, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Agnese Filippello, Francesca Urbano, Stefania Di Mauro, Alessandra Scamporrino, Antonino Di Pino, Roberto Scicali, Agata Maria Rabuazzo, Francesco Purrello, Salvatore Piro
Obesity and type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and impaired glucagon-like peptide-1 (GLP-1) secretion/function. Lipotoxicity, a chronic elevation of free fatty acids in the blood, could affect insulin-signaling in many peripheral tissues. To date, the effects of lipotoxicity on the insulin receptor and insulin resistance in the intestinal L-cells need to be elucidated. Moreover, recent observations indicate that L-cells may be able to process not only GLP-1 but also glucagon from proglucagon...
November 28, 2018: International Journal of Molecular Sciences
Hyoung Tae Kim, Alfred L Goldberg
The best-known function of ubiquitin-like (UBL) domains in proteins is to enable their binding to 26S proteasomes. The proteasome-associated deubiquitinating enzyme Usp14/UBP6 contains an N-terminal UBL domain and is an important regulator of proteasomal activity. Usp14 by itself represses multiple proteasomal activities but, upon binding a ubiquitin chain, Usp14 stimulates these activities and promotes ubiquitin-conjugate degradation. Here, we demonstrate that Usp14's UBL domain alone mimics this activation of proteasomes by ubiquitin chains...
November 28, 2018: Proceedings of the National Academy of Sciences of the United States of America
Linxia Song, Yi You, Theresa Evans-Nguyen
Many ambient desorption/ionization mass spectrometry (ADI-MS) techniques rely critically on thermal desorption. Mean-while, the analyte classes which are successfully studied by any particular ADI-MS are strongly dependent on the type of ionization source. Generally, spray-based ionization sources favor polar analytes, whereas plasma-based sources can be used for more hydrophobic analytes and more suitable for molecules with small molar masses. In the present work, classic atmos-pheric-pressure chemical ionization (APCI), is used...
November 27, 2018: Analytical Chemistry
Matthew D Shortridge, Paul T Wille, Alisha N Jones, Amy Davidson, Jasmina Bogdanovic, Eric Arts, Jonathan Karn, John A Robinson, Gabriele Varani
The HIV-1 trans-activator protein Tat binds the trans-activation response element (TAR) to facilitate recruitment of the super elongation complex (SEC) to enhance transcription of the integrated pro-viral genome. The Tat-TAR interaction is critical for viral replication and the emergence of the virus from the latent state, therefore, inhibiting this interaction has long been pursued to discover new anti-viral or latency reversal agents. However, discovering active compounds that directly target RNA with high affinity and selectivity remains a significant challenge; limiting pre-clinical development...
November 27, 2018: Nucleic Acids Research
Janarthanan Gopinathan, Insup Noh
Biomimetic medical materials are the biomaterials which mimic the important characteristic features of natural material/tissue structures or architectures and are mainly used in biomedical field for their applications in tissue regeneration, medical devices, biosensors and drug delivery. It is one of the leading research topics which have the ability to replace the existing biomaterials and medical devices and to development new biomaterials. The innovation and development in this research area are growing quickly because of the state-of-the-art techniques like nanobiotechnology, biosensors, tissue engineering and regenerative medicine, and 3D (bio)printing...
2018: Advances in Experimental Medicine and Biology
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