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Stability engineering

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https://www.readbyqxmd.com/read/28431327/dendrimer-conjugated-iron-oxide-nanoparticles-as-stimuli-responsive-drug-carriers-for-thermally-activated-chemotherapy-of-cancer
#1
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/28428038/non-invasive-tracking-of-hydrogel-degradation-using-upconversion-nanoparticles
#2
Yuqing Dong, Guorui Jin, Changchun Ji, Rongyan He, Min Lin, Xin Zhao, Ang Li, Tian Jian Lu, Feng Xu
Tracking the distribution and degradation of hydrogels in vivo is important for various applications including tissue engineering and drug delivery. Among various imaging modalities, fluorescence imaging has attracted intensive attention due to their high sensitivity, low cost and easy operation. Particularly, upconversion nanoparticles (UCNPs) that emit visible lights upon near-infrared (NIR) light excitation as tracking probes are promising in deciphering the fate of hydrogels after transplantation. Herein, we reported a facile and non-invasive in vivo hydrogel tracking method using UCNPs, where the degradation of hydrogels was determined using the decrease in fluorescence intensity from the UCNPs encapsulated in the hydrogels...
April 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28427644/optimization-of-ultrasonication-period-for-better-dispersion-and-stability-of-tio2-water-nanofluid
#3
I M Mahbubul, Elif Begum Elcioglu, R Saidur, M A Amalina
Nanofluids are promising in many fields, including engineering and medicine. Stability deterioration may be a critical constraint for potential applications of nanofluids. Proper ultrasonication can improve the stability, and possibility of the safe use of nanofluids in different applications. In this study, stability properties of TiO2-H2O nanofluid for varying ultrasonication durations were tested. The nanofluids were prepared through two-step method; and electron microscopies, with particle size distribution and zeta potential analyses were conducted for the evaluation of their stability...
July 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28426733/mini-g-proteins-novel-tools-for-studying-gpcrs-in-their-active-conformation
#4
Rony Nehmé, Byron Carpenter, Ankita Singhal, Annette Strege, Patricia C Edwards, Courtney F White, Haijuan Du, Reinhard Grisshammer, Christopher G Tate
Mini-G proteins are the engineered GTPase domains of Gα subunits. They couple to GPCRs and recapitulate the increase in agonist affinity observed upon coupling of a native heterotrimeric G protein. Given the small size and stability of mini-G proteins, and their ease of expression and purification, they are ideal for biophysical studies of GPCRs in their fully active state. The first mini-G protein developed was mini-Gs. Here we extend the family of mini-G proteins to include mini-Golf, mini-Gi1, mini-Go1 and the chimeras mini-Gs/q and mini-Gs/i...
2017: PloS One
https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#5
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep M ª Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance...
April 20, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28423276/supramolecular-%C3%AE-sheets-stabilized-protein-nanocarriers-for-drug-delivery-and-gene-transfection
#6
Yuan Ping, Dawei Ding, Ricardo Almeida Neves Sampayo Ramos, Harini Mohanram, Kanagavel Deepankumar, Jianqing Gao, Guping Tang, Ali Miserez
Suckerin proteins, recently discovered in the sucker ring teeth of squids, represent a family of promising structural biomacromolecules that can form supramolecular networks stabilized by nanoconfined β-sheets. Exploiting this feature as well as their specific amino acid composition, we demonstrate that artificial suckerin-19 (S-19) can be engineered into nanocarriers for efficient drug delivery and gene transfection in vitro and in vivo. First, we demonstrated that S-19 is self-assembled into β-sheet stabilized nanoparticles with controlled particle sizes of 100-200 nm that are able to encapsulate hydrophobic drugs for pH-dependent release in vitro, and that could effectively inhibit tumor growth in vivo...
April 19, 2017: ACS Nano
https://www.readbyqxmd.com/read/28422724/utilizing-combinatorial-engineering-to-develop-tie2-targeting-antagonistic-angiopoetin-2-ligands-as-candidates-for-anti-angiogenesis-therapy
#7
Tomer Shlamkovich, Lidan Aharon, William A Barton, Niv Papo
In many human cancers, the receptor tyrosine kinase (RTK) Tie2 plays important roles in mediating proliferation, survival, migration and angiogenesis. Thus, molecules that could potently inhibit activation of the Tie2 receptor would have a significant impact on cancer therapy. Nevertheless, attempts to develop Tie2-targeted inhibitors have met with little success, and there is currently no FDA-approved therapeutic selectively targeting Tie2. We used a combinatorial protein engineering approach to develop a new generation of angiopoietin (Ang) 2-derived Tie2 antagonists as potential cancer therapeutics and as tools to study angiogenesis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420742/synergistic-internal-ribosome-entry-site-microrna-based-approach-for-flavivirus-attenuation-and-live-vaccine-development
#8
Konstantin A Tsetsarkin, Guangping Liu, Evgeniya Volkova, Alexander G Pletnev
The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Using another flavivirus (Langat virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we describe a dual strategy for virus attenuation which synergistically accesses the specificity of microRNA (miRNA) genome targeting and the effectiveness of internal ribosome entry site (IRES) insertion. To increase the stability and immunogenicity of bicistronic LGTVs, we developed a novel approach in which the capsid (C) protein gene was relocated into the 3' noncoding region (NCR) and expressed under translational control from an IRES...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28419658/ancestral-haloalkane-dehalogenases-show-robustness-and-unique-substrate-specificity
#9
Petra Babkova, Eva Sebestova, Jan Brezovsky, Radka Chaloupkova, Jiri Damborsky
Ancestral sequence reconstruction (ASR) represents a powerful approach for empirical testing structure-function relationships of diverse proteins. We employed ASR to predict sequences of five ancestral haloalkane dehalogenases (HLDs) from the HLD-II subfamily. Genes encoding the inferred ancestral sequences were synthesized and expressed in Escherichia coli and the resurrected ancestral enzymes AncHLD1-5 were experimentally characterized. Strikingly, the ancestral HLDs exhibited significantly enhanced thermodynamic stability compared to extant enzymes (ΔTm up to 24 °C)...
April 17, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28418683/physical-characterization-of-tobramycin-inhalation-powder-ii-state-diagram-of-an-amorphous-engineered-particle-formulation
#10
Dan Miller, Trixie Tan, John Nakamura, Richard Malcolmson, Tom Tarara, Jeff Weers
Tobramycin Inhalation Powder (TIP) is a spray-dried engineered particle formulation used in TOBI® Podhaler®, a drug/device combination for treatment of cystic fibrosis. A TIP particle consists of two phases: amorphous, glassy tobramycin sulfate and a gel-phase phospholipid (DSPC). The objective of this work was to characterize both the amorphous and gel phases following exposure of TIP to a broad range of relative humidity and temperature. Because, in principle, changes in either particle morphology or the solid-state form of the drug could affect drug delivery or biopharmaceutical properties, understanding physical stability was critical to development and registration of this product...
April 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28416645/performance-stability-of-silicon-oxide-coated-plastic-parenteral-vials
#11
Christopher M Weikart, Carlo G Pantano, Jeff R Schallenberger
A new packaging system was developed for parenteral pharmaceuticals that combines the best attributes of plastic and glass without their respective drawbacks. This technological advancement is based on the synergy between high precision injection-molded plastics and plasma coating technology. The result is a shatter resistant, optically clear, low particulate and chemically durable packaging system. The demand for this product is driven by the expanding market, regulatory constraints and product recalls for injectable drugs and biologics packaged in traditional glass materials...
April 17, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/28416533/capturing-in-vivo-rna-transcriptional-dynamics-from-the-malaria-parasite-plasmodium-falciparum
#12
Heather J Painter, Manuela Carrasquilla, Manuel Llinás
To capture the transcriptional dynamics within proliferating cells, methods to differentiate nascent transcription from pre-existing mRNAs are desired. One approach is to label newly synthesized mRNA transcripts in vivo through the incorporation of modified pyrimidines. However, the human malaria parasite, Plasmodium falciparum, is incapable of pyrimidine salvage for mRNA biogenesis. To capture cellular mRNA dynamics during Plasmodium development, we engineered parasites that can salvage pyrimidines through the expression of a single bifunctional yeast fusion gene, cytosine deaminase/uracil phosphoribosyltransferase (FCU)...
April 17, 2017: Genome Research
https://www.readbyqxmd.com/read/28415480/improvement-of-mechanical-and-biological-properties-of-polycaprolactone-loaded-with-hydroxyapatite-and-halloysite-nanotubes
#13
E Torres, V Fombuena, A Vallés-Lluch, T Ellingham
Hydroxyapatite (HA) and Halloysite nanotubes (HNTs) percentages have been optimized in Polycaprolactone (PCL) polymeric matrices to improve mechanical, thermal and biological properties of the composites, thus, to be applied in bone tissue engineering or as fixation plates. Addition of HA guarantees a proper compatibility with human bone due to its osteoconductive and osteoinductive properties, facilitating bone regeneration in tissue engineering applications. Addition of HNTs ensures the presence of tubular structures for subsequent drug loading in their lumen, of molecules such as curcumin, acting as controlled drug delivery systems...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28415392/macroporous-modified-poly-vinyl-alcohol-hydrogels-with-charged-groups-for-tissue-engineering-preparation-and-in-vitro-evaluation
#14
Maria G Drozdova, Daria S Zaytseva-Zotova, Roman A Akasov, Anna S Golunova, Alexander A Artyukhov, Olga O Udartseva, Elena R Andreeva, Denis E Lisovyy, Michael I Shtilman, Elena A Markvicheva
Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical applications, including tissue engineering, due to their biocompatibility, high water solubility, low protein adsorption, and chemical stability. However, non-charged surface of PVA-based hydrogels is not optimal for cell adhesion and spreading. Here, cross-linked macroporous hydrogels based on low molecular weight acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol groups on the PVA with glycidyl methacrylate (GMA)...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28414710/using-the-pimeloyl-coa-synthetase-adenylation-fold-to-synthesize-fatty-acid-thioesters
#15
Menglu Wang, Lucile Moynié, Peter J Harrison, Van Kelly, Andrew Piper, James H Naismith, Dominic J Campopiano
Biotin is an essential vitamin in plants and mammals, functioning as the carbon dioxide carrier within central lipid metabolism. Bacterial pimeloyl-CoA synthetase (BioW) acts as a highly specific substrate-selection gate, ensuring the integrity of the carbon chain in biotin synthesis. BioW catalyzes the condensation of pimelic acid (C7 dicarboxylic acid) with CoASH in an ATP-dependent manner to form pimeloyl-CoA, the first dedicated biotin building block. Multiple structures of Bacillus subtilis BioW together capture all three substrates, as well as the intermediate pimeloyl-adenylate and product pyrophosphate (PPi), indicating that the enzyme uses an internal ruler to select the correct dicarboxylic acid substrate...
April 17, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28413876/generation-of-an-orthogonal-protein-protein-interface-with-a-noncanonical-amino-acid
#16
Minseob Koh, Fariborz Nasertorabi, Gye Won Han, Raymond C Stevens, Peter G Schultz
We have engineered the protein interface of the Escherichia coli chorismate mutase (EcCM) homodimer to be dependent on incorporation of a noncanonical amino acid (ncAA) at residue 72. The large hydrophobic amino acid p-benzoyl phenylalanine (pBzF) was substituted for Tyr72, which led to a catalytically inactive protein. A library of five residues (Leu25', Arg29', Leu76, Ile80' and Asp83') surrounding pBzF72 was generated and subjected to a growth based selection in a chorismate mutase deficient strain. An EcCM variant (Phe25', pBzF72, Thr76, Gly80' and Tyr83') forms a stable homodimer, has catalytic activity similar to the wild type enzyme, and unfolds with a Tm of 53 °C...
April 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28413260/missing-linkers-an-alternative-pathway-to-uio-66-electronic-structure-engineering
#17
Arthur De Vos, Kevin Hendrickx, Pascal Van Der Voort, Veronique Van Speybroeck, Kurt Lejaeghere
UiO-66 is a promising metal-organic framework for photocatalytic applications. However, the ligand-to-metal charge transfer of an excited electron is inefficient in the pristine material. Herein, we assess the influence of missing linker defects on the electronic structure of UiO-66 and discuss their ability to improve ligand-to-metal charge transfer. Using a new defect classification system, which is transparent and easily extendable, we identify the most promising photocatalysts by considering both relative stability and electronic structure...
April 11, 2017: Chemistry of Materials: a Publication of the American Chemical Society
https://www.readbyqxmd.com/read/28412223/bioengineered-robust-hybrid-hydrogels-enrich-the-stability-and-efficacy-of-biological-drugs
#18
Moon Soo Gil, Jinhwan Cho, Thavasyappan Thambi, V H Giang Phan, Inchan Kwon, Doo Sung Lee
Biological drugs are exquisitely tailored components offering the advantages of high specificity and efficacy that are considered safe for treating diseases. Nevertheless, the effectiveness of biological drugs is limited by their inherent short biological half-life and poor stability in vivo. Herein, we engineered a novel delivery platform based on hybrid injectable hydrogels, in which pH- and temperature-responsive biodegradable copolymers were site-specifically coupled to the sulfhydryl group of human serum albumin, which effectively enhances the stability and circulation half-life of the biological drug, recombinant uricase enzyme (Uox)...
April 12, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28411867/a-rapid-approach-for-measuring-silver-nanoparticle-concentration-and-dissolution-in-seawater-by-uv-vis
#19
Mithun Sikder, Jamie R Lead, G Thomas Chandler, Mohammed Baalousha
Detection and quantification of engineered nanoparticles (NPs) in environmental systems is challenging and requires sophisticated analytical equipment. Furthermore, dissolution is an important environmental transformation process for silver nanoparticles (AgNPs) which affects the size, speciation and concentration of AgNPs in natural water systems. Herein, we present a simple approach for the detection, quantification and measurement of dissolution of PVP-coated AgNPs (PVP-AgNPs) based on monitoring their optical properties (extinction spectra) using UV-vis spectroscopy...
April 12, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28411650/armoring-enzymes-by-metal-organic-frameworks-by-the-coprecipitation-method
#20
Miao Hou, Jun Ge
Enzymatic processes have great potential for applications in industrial biocatalysis, biosensing, and biomedical engineering. However, poor stability and difficulty in the reuse of enzymes still create challenges for their use in catalysis and other applications. In recent years, enzyme-incorporated metal-organic frameworks (enzyme@MOF) have emerged as a new type of armored enzymes and are thought to be an appealing solution to the above challenges. To date, the preparation of enzyme-MOF composites can be divided into three categories, including physical adsorption, covalent conjugation, and coprecipitation...
2017: Methods in Enzymology
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