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https://www.readbyqxmd.com/read/28627455/gemcitabine-vitamin-e-conjugates-synthesis-characterization-entrapment-into-nanoemulsions-and-in-vitro-deamination-and-antitumor-activity
#1
Ahmed Abu-Fayyad, Sami Nazzal
Gemcitabine is the first line therapy for pancreatic cancer. It is, however, extensively metabolized to the inactive form by deamination enzymatic reaction. Conjugation of gemcitabine with fatty acids on its 4-amino group was found to protect it from deamination deactivation reaction. The objective of the present study was to test the in-vitro anticancer activity of gemcitabine conjugated to the γ-tocotrienol isomer of vitamin E against pancreatic tumor cells. This objective was based on reported studies in which it was demonstrated that free tocotrienol isomers of vitamin E can potentiate the anticancer activity of gemcitabine...
June 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28611396/coupling-neutron-reflectivity-with-cell-free-protein-synthesis-to-probe-membrane-protein-structure-in-supported-bilayers
#2
Thomas Soranzo, Donald K Martin, Jean-Luc Lenormand, Erik B Watkins
The structure of the p7 viroporin, an oligomeric membrane protein ion channel involved in the assembly and release of the hepatitis C virus, was determined from proteins expressed and inserted directly into supported model lipid membranes using cell-free protein expression. Cell-free protein expression allowed (i ) high protein concentration in the membrane, (ii ) control of the protein's isotopic constitution, and (iii ) control over the lipid environment available to the protein. Here, we used cell-free protein synthesis to directly incorporate the hepatitis C virus (HCV) p7 protein into supported lipid bilayers formed from physiologically relevant lipids (POPC or asolectin) for both direct structural measurements using neutron reflectivity (NR) and conductance measurements using electrical impedance spectroscopy (EIS)...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607419/two-step-atp-driven-opening-of-cohesin-head
#3
Íñigo Marcos-Alcalde, Jesús I Mendieta-Moreno, Beatriz Puisac, María Concepción Gil-Rodríguez, María Hernández-Marcos, Diego Soler-Polo, Feliciano J Ramos, José Ortega, Juan Pié, Jesús Mendieta, Paulino Gómez-Puertas
The cohesin ring is a protein complex composed of four core subunits: Smc1A, Smc3, Rad21 and Stag1/2. It is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation. Opening of the ring occurs at the "head" structure, formed of the ATPase domains of Smc1A and Smc3 and Rad21. We investigate the mechanisms of the cohesin ring opening using techniques of free molecular dynamics (MD), steered MD and quantum mechanics/molecular mechanics MD (QM/MM MD). The study allows the thorough analysis of the opening events at the atomic scale: i) ATP hydrolysis at the Smc1A site, evaluating the role of the carboxy-terminal domain of Rad21 in the process; ii) the activation of the Smc3 site potentially mediated by the movement of specific amino acids; and iii) opening of the head domains after the two ATP hydrolysis events...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606519/folate-conjugated-thermosensitive-o-maleoyl-modified-chitosan-micellar-nanoparticles-for-targeted-delivery-of-erlotinib
#4
Marziyeh Fathi, Parham Sahandi Zangabad, Ayuob Aghanejad, Jaleh Barar, Hamid Erfan-Niya, Yadollah Omidi
In the present work, new self-assembled nanoparticles (NPs) were engineered using biocompatible and biodegradable natural polymer, chitosan (CS). The complexation of CS with sodium dodecyl sulfate (SDS) facilitated the regioselective chemical modification of CS hydroxyl groups with maleic anhydride, and produced polymerizable precursor of CS that was further grafted with N-isopropylacrylamide (NIPAAm) as temperature-sensitive moiety and oleic acid (OA) as hydrophobic monomer. After removal of SDS complex, the free amino groups were functionalized with folic acid (FA) to form folate-(PNIPAAm-co-OA)-g-CS micellar NPs...
September 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28596363/polymeric-peptide-pigments-with-sequence-encoded-properties
#5
Ayala Lampel, Scott A McPhee, Hang-Ah Park, Gary G Scott, Sunita Humagain, Doeke R Hekstra, Barney Yoo, Pim W J M Frederix, Tai-De Li, Rinat R Abzalimov, Steven G Greenbaum, Tell Tuttle, Chunhua Hu, Christopher J Bettinger, Rein V Ulijn
Melanins are a family of heterogeneous polymeric pigments that provide ultraviolet (UV) light protection, structural support, coloration, and free radical scavenging. Formed by oxidative oligomerization of catecholic small molecules, the physical properties of melanins are influenced by covalent and noncovalent disorder. We report the use of tyrosine-containing tripeptides as tunable precursors for polymeric pigments. In these structures, phenols are presented in a (supra-)molecular context dictated by the positions of the amino acids in the peptide sequence...
June 9, 2017: Science
https://www.readbyqxmd.com/read/28595008/rapid-and-convenient-oxidative-release-of-thiol-conjugated-forms-of-microcystins-for-chemical-analysis
#6
Christopher O Miles
Microcystins are potent cyclic heptapeptide toxins found in some cyanobacteria, and usually contain an α,β-unsaturated carbonyl group that is readily conjugated to thiol-containing amino acids, peptides and proteins in vivo and in vitro. Methods for deconjugating these types of adducts have recently been reported, but the reactions are slow or result in derivatized microcystins. Mercaptoethanol derivatives of a range of microcystins were therefore used as model compounds to develop deconjugation procedures in which the dialkyl sulfide linkage was oxidized to a sulfoxide or sulfone that, when treated with base, rapidly eliminated the adducted thiol as its sulfenate or sulfinate via β-elimination to afford free microcystins with the α,β-unsaturated carbonyl group intact...
June 8, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28592485/energetics-of-side-chain-partitioning-of-%C3%AE-signal-residues-in-unassisted-folding-of-a-transmembrane-%C3%AE-barrel-protein
#7
Bharat Ramasubramanian Iyer, Punit Zadafiya, Pallavi Vijay Vetal, Radhakrishnan Mahalakshmi
The free energy of water-to-interface amino acid partitioning is a major contributing factor in membrane protein folding and stability. The interface residues at the C-terminus of transmembrane β-barrels form the β-signal motif required for assisted β-barrel assembly in vivo, but are believed to be less important for β-barrel assembly in vitro Here, we experimentally measured the thermodynamic contribution of all 20 amino acids at the β-signal motif to the unassisted folding of the model β-barrel protein PagP...
June 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28588135/spatial-distribution-and-ribosome-binding-dynamics-of-ef-p-in-live-escherichia%C3%A2-coli
#8
Sonisilpa Mohapatra, Heejun Choi, Xueliang Ge, Suparna Sanyal, James C Weisshaar
In vitro assays find that ribosomes form peptide bonds to proline (Pro) residues more slowly than to other residues. Ribosome profiling shows that stalling at Pro-Pro-X triplets is especially severe but is largely alleviated in Escherichia coli by the action of elongation factor EF-P. EF-P and its eukaryotic/archaeal homolog IF5A enhance the peptidyl transfer step of elongation. Here, a superresolution fluorescence localization and tracking study of EF-P-mEos2 in live E. coli provides the first in vivo information about the spatial distribution and on-off binding kinetics of EF-P...
June 6, 2017: MBio
https://www.readbyqxmd.com/read/28588048/the-sphingosine-1-phosphate-break-down-product-2e-hexadecenal-forms-protein-adducts-and-glutathione-conjugates-in-vitro
#9
Fabian Schumacher, Corinna Neuber, Hannah Finke, Kai Nieschalke, Jessica Baesler, Erich Gulbins, Burkhard Kleuser
Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes such as cell proliferation and apoptosis, can be irreversibly cleaved by the S1P lyase, yielding phosphoethanolamine and (2E)-hexadecenal (2EHD). The latter metabolite, an α,β-unsaturated fatty aldehyde, may be susceptible to nucleophilic attack by cellular biomolecules. Hence, we studied whether 2EHD forms reaction products with glutathione (GSH) and proteins in vitro Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and stable isotopically labeled reference material, we identified a total of nine novel reaction products of 2EHD in a cell-free approach: two GSH conjugates and seven L-amino acid adducts...
June 6, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28577408/dendrimer-functionalized-electrospun-nanofibres-as-dual-action-water-treatment-membranes
#10
Georgiana Amariei, Javier Santiago-Morales, Karina Boltes, Pedro Letón, Isabel Iriepa, Ignacio Moraleda, Amadeo R Fernández-Alba, Roberto Rosal
This work reports the preparation of composite electrospun membranes combining antimicrobial action with the capacity of retaining low-molecular weight non-polar pollutants. The membranes were electrospun blends of polyvinyl alcohol (PVA) and poly(acrylic acid) (PAA) stabilized using heat curing. The membranes were functionalized by grafting amino-terminated poly(amidoamine) (PAMAM) G3 dendrimers. The antimicrobial effect was assessed using strains of Escherichia coli and Staphylococcus aureus by tracking their capacity to form new colonies and their metabolic impairment upon contact with membranes...
May 31, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28569194/severe-child-form-of-primary-hyperoxaluria-type-2-a-case-report-revealing-consequence-of-grhpr-deficiency-on-metabolism
#11
Jana Konkoľová, Ján Chandoga, Juraj Kováčik, Marcel Repiský, Veronika Kramarová, Ivana Paučinová, Daniel Böhmer
BACKGROUND: Primary hyperoxaluria type 2 is a rare monogenic disorder inherited in an autosomal recessive pattern. It results from the absence of the enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR). As a consequence of deficient enzyme activity, excessive amounts of oxalate and L-glycerate are excreted in the urine, and are a source for the formation of calcium oxalate stones that result in recurrent nephrolithiasis and less frequently nephrocalcinosis. CASE PRESENTATION: We report a case of a 10-month-old patient diagnosed with urolithiasis...
May 31, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28504581/bacillus-coagulans-gbi-30-6086-increases-plant-protein-digestion-in-a-dynamic-computer-controlled-in-vitro-model-of-the-small-intestine-tim-1
#12
D Keller, R Van Dinter, H Cash, S Farmer, K Venema
The aim of this study was to assess the potential of the probiotic Bacillus coagulans GBI-30, 6086 [GanedenBC(30)] (BC30) to aid in protein digestion of alimentary plant proteins. To test this, three plant proteins, from pea, soy and rice, were digested in a validated in vitro model of the stomach and small intestine (TIM-1) in the absence and in the presence of BC30. Samples were taken from the TIM-1 fractions that mimic uptake of amino acids by the host and analysed for α-amino nitrogen (AAN) and total nitrogen (TN)...
May 15, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28502169/direct-conjugation-of-emerging-contaminants-in-arabidopsis-indication-for-an-overlooked-risk-in-plants
#13
Qiuguo Fu, Jianbo Zhang, Dan Borchardt, Daniel Schlenk, Jay Gan
Agricultural use of treated wastewater, biosolids, and animal wastes introduces a multitude of contaminants of emerging concerns (CECs) into the soil-plant system. The potential for food crops to accumulate CECs depends largely on their metabolism in plants, which at present is poorly understood. Here, we evaluated the metabolism of naproxen and ibuprofen, two of the most-used human drugs from the Profen family, in Arabidopsis thaliana cells and the Arabidopsis plant. The complementary use of high-resolution mass spectrometry and (14)C labeling allowed the characterization of both free and conjugated metabolites, as well as nonextractable residues...
June 6, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28500593/assessment-of-protein-carbonylation-and-protein-tyrosine-phosphatase-ptp-oxidation-in-vascular-smooth-muscle-cells-vsmcs-using-immunoblotting-approaches
#14
Sofia Tsiropoulou, Rhian M Touyz
Post-translational modification of proteins, such as phosphorylation and oxidation, plays a major role in cellular signaling by influencing protein structure and function. In vascular cells, in addition to influencing phosphorylation, angiotensin II (Ang II) induces oxidation of proteins, important in redox signaling in the cardiovascular and renal systems. The present chapter describes immunoblotting approaches to assess irreversible protein carbonylation and protein tyrosine phosphatase (PTPs) oxidation status in the proteome of vascular smooth muscle cells (VSMC)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28496969/synthetic-approaches-to-nucleopeptides-containing-all-four-nucleobases-and-nucleic-acid-binding-studies-on-a-mixed-sequence-nucleo-oligolysine
#15
Giovanni N Roviello, Domenica Musumeci
In this article we describe two solid-phase synthetic routes to obtain a nucleo-oligolysine α-peptide containing all four natural nucleobases. The first one is based on the oligomerization of the nucleobase-containing monomers, easily synthesized as herein described. The second strategy has the advantage of avoiding the solution synthesis of the monomeric building blocks, leading to the final nucleopeptide by direct solid-phase couplings of the suitably protected nucleobases with the free amino groups on the growing peptide chain still anchored to the resin...
July 16, 2016: RSC Advances
https://www.readbyqxmd.com/read/28496122/structural-insights-into-a-20-8-kda-tegumental-allergen-like-tal-protein-from-clonorchis-sinensis
#16
Chang Hwa Jo, Jonghyeon Son, Sulhee Kim, Takashi Oda, Jaehoon Kim, Myoung-Ro Lee, Mamoru Sato, Hyun Tae Kim, Satoru Unzai, Sam-Yong Park, Kwang Yeon Hwang
Survival of Clonorchis sinensis, a cause of human clonorchiasis, requires tegument proteins, which are localized to the tegumental outer surface membrane. These proteins play an important role in a host response and parasite survival. Thus, these proteins are interesting molecular targets for vaccine and drug development. Here, we have determined two crystal structures of the calmodulin like domain (amino acid [aa] positions 1-81) and dynein light chain (DLC)-like domain (aa 83-177) of a 20.8-kDa tegumental-allergen-like protein from Clonorchis sinensis (CsTAL3)...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489381/molecular-mechanism-of-the-reaction-specificity-in-threonine-synthase-importance-of-the-substrate-conformations
#17
Yuzuru Ujiie, Wataru Tanaka, Kyohei Hanaoka, Ryuhei Harada, Megumi Kayanuma, Mitsuo Shoji, Takeshi Murakawa, Toyokazu Ishida, Yasuteru Shigeta, Hideyuki Hayashi
Threonine synthase (ThrS) catalyzes the final chemical reaction of l-threonine biosynthesis from its precursor, O-phospho-l-homoserine. As the phosphate ion generated in its former half reaction assists its latter reaction, ThrS is recognized as one of the best examples of product-assisted catalysis. In our previous QM/MM study, the chemical reactions for the latter half reactions, which are critical for the product-assisted catalysis, were revealed. However, accurate free energy changes caused by the conformational ensembles and entrance of water molecules into the active site are unknown...
May 24, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28487079/d-aspartic-acid-ameliorates-painful-and-neuropsychiatric-changes-and-reduces-%C3%AE-amyloid-a%C3%AE-1-42-peptide-in-a-long-lasting-model-of-neuropathic-pain
#18
Antimo D'Aniello, Livio Luongo, Rosaria Romano, Monica Iannotta, Ida Marabese, Serena Boccella, Carmela Belardo, Vito de Novellis, Claudio Arra, Antonio Barbieri, Biagio D'Aniello, Anna Scandurra, Laura Migliozzi, George Fisher, Francesca Guida, Sabatino Maione
Depressive symptoms and other neuropsychiatric dysfunctions are common in neurodegenerative disorders, including chronic pain and dementia. A correlation between the β-amyloid protein accumulation and the development of depression has been suggested, however the underlying mechanisms are unknown. d-Aspartate (d-Asp) is a free d-amino acid found in the mammalian brain and involved in neurological and psychiatric processes, such as cognition and affective disorders. In this study we have investigated the effects of a repeated treatment with d-Asp in a long-lasting (12 months) model of neuropathic pain, the spared nerve injury (SNI), in mice...
May 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28482109/organic-and-inorganic-nitrogen-uptake-by-21-dominant-tree-species-in-temperate-and-tropical-forests
#19
Min Liu, Changcheng Li, Xingliang Xu, Wolfgang Wanek, Ning Jiang, Huimin Wang, Xiaodong Yang
Evidence shows that many tree species can take up organic nitrogen (N) in the form of free amino acids from soils, but few studies have been conducted to compare organic and inorganic N uptake patterns in temperate and tropical tree species in relation to mycorrhizal status and successional state. We labeled intact tree roots by brief 15N exposures using field hydroponic experiments in a temperate forest and a tropical forest in China. A total of 21 dominant tree species were investigated, 8 in the temperate forest and 13 in the tropical forest...
May 8, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28480401/prospective-effect-of-red-algae-actinotrichia-fragilis-against-some-osteoarthritis-aetiology
#20
Amany A Sayed, Shimaa A Sadek, Amel M Solimán, Mohamed Marzouk
BACKGROUND: Osteoarthritis (OA) is a progressive disease characterized by joints pain and articular cartilage destruction. Most of the current treatment strategies for OA are effective for symptoms relief but are accompanied with adverse side effect. Thus, the present investigation aims to evaluate the potential influence of red algae, Actinotrichia fragilis, in the dry powder form (AFP) or gel form (AFG) on some relevant factors of OA progression as well as assess its safety through in vitro and in vivo experiments...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
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