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https://www.readbyqxmd.com/read/28431354/first-example-of-peptides-targeting-the-dimer-interface-of-leishmania-infantum-trypanothione-reductase-with-potent-in%C3%A2-vitro-antileishmanial-activity
#1
Marta Ruiz-Santaquiteria, Pedro A Sánchez-Murcia, Miguel A Toro, Héctor de Lucio, Kilian Jesús Gutiérrez, Sonia de Castro, Filipa A C Carneiro, Federico Gago, Antonio Jiménez-Ruiz, María-José Camarasa, Sonsoles Velázquez
A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH2 (Toro et al. ChemBioChem2013) has been designed and synthesized by introduction of the lactam between amino acid side chains that are separated by one helical turn (i, i+4). All of these compounds were tested in vitro as both dimerization and enzyme inhibitors of Leishmania infantum trypanothione reductase (Li-TryR). Three of the 13-mer cyclic peptide derivatives (3, 4 and 6) inhibited the oxidoreductase activity of Li-TryR in the low micromolar range and they also disrupted enzyme dimerization...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431327/dendrimer-conjugated-iron-oxide-nanoparticles-as-stimuli-responsive-drug-carriers-for-thermally-activated-chemotherapy-of-cancer
#2
Saumya Nigam, Dhirendra Bahadur
In recent years, functional nanomaterials have found an appreciable place in the understanding and treatment of cancer. This work demonstrates the fabrication and characterization of a new class of cationic, biocompatible, peptide dendrimers, which were then used for stabilizing and functionalizing magnetite nanoparticles for combinatorial therapy of cancer. The synthesized peptide dendrimers have an edge over the widely used PAMAM dendrimers due to better biocompatibility and negligible cytotoxicity of their degradation products...
April 13, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28431319/response-of-plasma-glucagon-like-peptide-2-to-feeding-pattern-and-intraruminal-administration-of-volatile-fatty-acids-in-sheep
#3
M Elsabagh, Y Inabu, T Obitsu, T Sugino
Glucagon-like peptide-2 (GLP-2), a gut peptide secreted by enteroendocrine L cells, has recently been identified as a key regulator of intestinal growth and absorptive function in ruminants. However, reports on GLP-2 secretion are few, and more information regarding its secretion dynamics is needed. In this study, two experiments were conducted to elucidate the daily rhythm of GLP-2 secretion in response to feeding regimen and to investigate the effect of volatile fatty acids (VFA) on GLP-2 release in sheep...
March 11, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28431213/genome-mining-unearths-a-hybrid-nonribosomal-peptide-synthetase-like-pteridine-synthase-biosynthetic-gene-cluster
#4
Hyun Bong Park, Corey E Perez, Karl W Barber, Jesse Rinehart, Jason M Crawford
Nonribosomal peptides represent a large class of metabolites with pharmaceutical relevance. Pteridines, such as pterins, folates, and flavins, are heterocyclic metabolites that often serve as redox-active cofactors. The biosynthetic machineries for construction of these distinct classes of small molecules operate independently in the cell. Here, we discovered an unprecedented nonribosomal peptide synthetase-like-pteridine synthase hybrid biosynthetic gene cluster in Photorhabdus luminescens using genome synteny analysis...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28431161/engineering-a-high-affinity-peptide-binding-site-into-the-anti-cea-mab-m5a
#5
Cindy Zer, Kendra N Avery, Kassondra Meyer, Leah Goodstein, Krzysztof P Bzymek, Gagandeep Singh, John C Williams
We have previously identified a cyclic peptide called meditope which binds to the central cavity of the Fab portion of cetuximab and shown that this peptide binding site can be grafted, or 'meditope-enabled', onto trastuzumab. This peptide has been shown to act as a hitch for the non-covalent attachment of imaging agents to meditope-enabled antibodies. Herein, we explore the process of grafting this peptide binding site onto M5A, an anti-CEA antibody in clinical trials for cancer diagnostics. In order to explore the contributions of the amino acids, we sequentially introduced pairs of amino acid substitutions into the Fab and then we reverse-substituted key residues in the presence of the other substitutions...
April 19, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28430981/central-nervous-system-glp-1-receptors-regulate-islet-hormone-secretion-and-glucose-homeostasis-in-male-rats
#6
Lene Jessen, Eric P Smith, Yvonne Ulrich-Lai, James P Herman, Randy J Seeley, Darleen Sandoval, David D'Alessio
The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1r) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430962/ulk1-prevents-cardiac-dysfunction-in-obesity-through-autophagy-meditated-regulation-of-lipid-metabolism
#7
Minae An, Dong-Ryeol Ryu, Jang Won Park, Ji Ha Choi, Eun-Mi Park, Kyung Eun Lee, Minna Woo, Minsuk Kim
Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28430903/co-storage-of-enteroendocrine-hormones-evaluated-at-the-cell-and-subcellular-levels-in-male-mice
#8
Linda J Fothergill, Brid Callaghan, Billie Hunne, David M Bravo, John B Furness
Recent studies reveal complex patterns of hormone co-expression within enteroendocrine cells (EEC), contrary to the traditional view that gut hormones are expressed individually in EEC. Moreover, different hormones have been found in separate subcellular vesicles. However, detailed analysis of relative expression of multiple hormones has not been made. Subcellular studies have been confined to peptide hormones, and have not included the indolamine, 5-HT, or the neuroendocrine protein, chromogranin A (CgA). In the present work, co-expression of 5-HT, CgA, secretin, CCK, ghrelin, and GLP-1 in mouse duodenum was quantified at a cellular and subcellular level by semi-automated cell counting and quantitative vesicle measurements...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430871/cluspro-peptidock-efficient-global-docking-of-peptide-recognition-motifs-using-fft
#9
Kathryn A Porter, Bing Xia, Dmitri Beglov, Tanggis Bohnuud, Nawsad Alam, Ora Schueler-Furman, Dima Kozakov
Summary: We present an approach for the efficient docking of peptide motifs to their free receptor structures. Using a motif based search, we can retrieve structural fragments from the Protein Data Bank (PDB) that are very similar to the peptide's final, bound conformation. We use a Fast Fourier Transform (FFT) based docking method to quickly perform global rigid body docking of these fragments to the receptor. According to CAPRI peptide docking criteria, an acceptable conformation can often be found among the top-ranking predictions...
April 18, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28430869/inhibition-of-the-p2x7-panx1-complex-suppresses-spreading-depolarization-and-neuroinflammation
#10
Shih-Pin Chen, Tao Qin, Jessica L Seidel, Yi Zheng, Matthias Eikermann, Michel D Ferrari, Arn M J M van den Maagdenberg, Michael A Moskowitz, Cenk Ayata, Katharina Eikermann-Haerter
Spreading depolarization is a wave of neuronal and glial depolarization. Within minutes after spreading depolarization, the neuronal hemichannel pannexin 1 (PANX1) opens and forms a pore complex with the ligand-gated cation channel P2X7, allowing the release of excitatory neurotransmitters to sustain spreading depolarization and activate neuroinflammation. Here, we explore the hypothesis that the P2X7-PANX1 pore complex is a critical determinant of spreading depolarization susceptibility with important consequences for neuroinflammation and trigeminovascular activation...
April 20, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430864/the-gnih-lpxrfa-system-s-regulation-of-reproduction-in-the-brain-pituitary-axis-of-the-zebrafish-danio-rerio
#11
Olivia Smith Spicer, Nilli Zmora, Ten-Tsao Wong, Matan Golan, Berta Levavi-Sivan, Yoav Gothilf, Yonathan Zohar
Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (Lpxrfa peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28430446/piecing-together-the-allosteric-patterns-of-chaperonin-groel
#12
Jin Chen, Qian Zhang, Weitong Ren, Wenfei Li
Despite considerable effort, elucidating allostery of large macromolecular assemblies at a molecular level in solution remains technically challenging due to its structural complexity. Here we have employed an approach combining amide backbone hydrogen/deuterium exchange coupled with mass spectrometry, fluorescence spectroscopy and molecular simulations to characterize allosteric patterns of chaperonin GroEL, a ~800 kDa tetradecamer from E. coli. Using available crystal structures of GroEL, we quantitatively map out GroEL allosteric changes in solution by resolving exchange behaviors of 133 overlapping proteolytic peptides with more than 95% sequence coverage...
April 21, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28430426/the-rosetta-all-atom-energy-function-for-macromolecular-modeling-and-design
#13
Rebecca Faye Alford, Andrew Leaver-Fay, Jeliazko R Jeliazkov, Matthew J O'Meara, Frank P DiMaio, Hahnbeom Park, Maxim V Shapovalov, P Douglas Renfrew, Vikram Khipple Mulligan, Kalli Kappel, Jason W Labonte, Michael Steven Pacella, Richard Bonneau, Philip Bradley, Roland L Dunbrack, Rhiju Das, David Baker, Brian Kuhlman, Tanja Kortemme, Jeffrey J Gray
Over the past decade, the Rosetta biomolecular modeling suite has informed diverse biological questions and engineering challenges ranging from interpretation of low-resolution structural data to design of nanomaterials, protein therapeutics, and vaccines. Central to Rosetta's success is the energy function: a model parameterized from small molecule and X-ray crystal structure data used to approximate the energy associated with each biomolecule conformation. This paper describes the mathematical models and physical concepts that underlie the latest Rosetta Energy Function, REF15...
April 21, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28430394/structure-based-design-of-a-new-scaffold-for-cell-penetrating-peptidic-inhibitors-of-the-histone-demethylase-phf8
#14
Jerzy Dorosz, Lars Olsen, Signe Teuber Seger, Cornelia Steinhauer, Giorgos Bouras, Charlotte Helgstrand, Anders Wiuf, Michael Gajhede
The histone demethylase PHF8 catalyzes demethylation of mono- and di-methylated lysine 9 on histone H3 (H3K9me1/2) and is a transcriptional activator involved in development and cancer. Affinity and specificity of PHF8 towards H3K9me2 substrate is affected by interaction with both the catalytic domain and a PHD reader domain. The latter specifically recognizes tri-methylated lysine 4 on histone H3. A fragment of the histone H3 tail with tri-methylated lysine 4 was used as template for structure based design of a cyclic, cell-penetrating peptide that exhibits micromolar binding affinity to PHF8 in biochemical assays...
April 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28430386/peptidome-analysis-of-human-serum-from-normal-and-preeclamptic-pregnancies
#15
Xiaonan Dai, Xuejing Song, Can Rui, Li Meng, Xuan Xue, Hongjuan Ding, Rong Shen, Jun Li, Jingyun Li, Yuanqing Lu, Wei Long
Preeclampsia is a kind of disease that severely harms the health of pregnant women and infants. To better understand the molecular mechanisms involved in preeclampsia, we used liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to construct a comparative peptidomic profiling of human serum between normal and preeclamptic pregnancies. A total of 201 peptides were confidently identified, with 21 up-regulated and 3 down-regulated. Further analysis indicated that these differentially expressed peptides correlate with enzyme regulator activity, biological regulation, and coagulation cascades occurring during pathological changes of preeclampsia...
April 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28430371/evaluation-of-circulating-zonulin-as-a-potential-marker-in-the-pathogenesis-of-nonalcoholic-fatty-liver-disease
#16
Olfat M Hendy, Maha M Elsabaawy, Mona M Aref, Fatma M Khalaf, Abdel Moaty A Oda, Helmy M El Shazly
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested...
April 21, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28430366/cyclic-rgd-penta-peptides-crgdyk-derivatized-with-cyclopentadienyl-complexes-of-technetium-and-rhenium-as-radiopharmaceutical-probes
#17
Qaisar Nadeem, Yunjun Shen, Muhammad Farooq Warsi, Gulfam Nasar, Muhammad Abdul Qadir, Roger Alberto
The present study reports the syntheses of half-sandwich complexes of the type [M(η(5) -C5 H4 CONH-R)(CO)3 ] (M = Re,(99m) Tc;R = cyclic RGD peptide (cRGDyK) for potential imaging of αv β3 integrin expression. The (99m) Tc complex was prepared directly from the reaction of [(99m) Tc(OH2 )3 (CO)3 ](+) with cRGDyK, doubly conjugated to Thiele's acid [(C5 H5 COOH)2 ] in water. This approach extends the viability of metal-mediated retro Diels-Alder reactions for the preparation of small molecules such as linear tripeptides to a more complex cyclic peptide carrying a [(η(5) -C5 H4 )(99m) Tc(CO)3 ] tag...
April 21, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28430363/cerebrolysin-for-acute-ischaemic-stroke
#18
REVIEW
Liliya Eugenevna Ziganshina, Tatyana Abakumova, Ludivine Vernay
BACKGROUND: Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. OBJECTIVES: To assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke. SEARCH METHODS: In May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28430207/corrigendum-construction-and-immunogenicity-of-a-recombinant-swinepox-virus-expressing-a-multi-epitope-peptide-for-porcine-reproductive-and-respiratory-syndrome-virus
#19
Huixing Lin, Zhe Ma, Xin Hou, Lei Chen, Hongjie Fan
No abstract text is available yet for this article.
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28430192/a-monodisperse-transmembrane-%C3%AE-helical-peptide-barrel
#20
Kozhinjampara R Mahendran, Ai Niitsu, Lingbing Kong, Andrew R Thomson, Richard B Sessions, Derek N Woolfson, Hagan Bayley
The fabrication of monodisperse transmembrane barrels formed from short synthetic peptides has not been demonstrated previously. This is in part because of the complexity of the interactions between peptides and lipids within the hydrophobic environment of a membrane. Here we report the formation of a transmembrane pore through the self-assembly of 35 amino acid α-helical peptides. The design of the peptides is based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza. By using single-channel current recording, we define discrete assembly intermediates and show that the pore is most probably a helix barrel that contains eight D4 peptides arranged in parallel...
May 2017: Nature Chemistry
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