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https://www.readbyqxmd.com/read/27914064/computational-tools-for-aiding-rational-antibody-design
#1
Konrad Krawczyk, James Dunbar, Charlotte M Deane
Antibodies are a group of proteins responsible for mediating immune reactions in vertebrates. They are able to bind a variety of structural motifs on noxious molecules tagging them for elimination from the organism. As a result of their versatile binding properties, antibodies are currently one of the most important classes of biopharmaceuticals. In this chapter, we discuss how knowledge-based computational methods can aid experimentalists in the development of potent antibodies. When using common experimental methods for antibody development, we often know the sequence of an antibody that binds to our molecule, antigen, of interest...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27911829/supramolecular-pegylation-of-biopharmaceuticals
#2
Matthew J Webber, Eric A Appel, Brittany Vinciguerra, Abel B Cortinas, Lavanya S Thapa, Siddharth Jhunjhunwala, Lyle Isaacs, Robert Langer, Daniel G Anderson
The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27910726/the-effect-of-deuterium-oxide-on-the-conformational-stability-and-aggregation-of-bovine-serum-albumin
#3
Mouhamad Reslan, Veysel Kayser
Protein aggregation is a significant problem affecting the integrity of proteins, and is a major hindrance to the development of biopharmaceutical products. Deuterium Oxide (D2O), widely used in protein characterization studies, has been shown to promote protein aggregation when used as a substitute for water in most buffered protein solutions; however, a few studies have reported minor improvements in melting point temperatures for some proteins. Our study aims to investigate the effect of D2O on protein stability, using bovine serum albumin (BSA) as a model...
December 2, 2016: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/27908674/renaissance-of-protein-crystallization-and-precipitation-in-biopharmaceuticals-purification
#4
REVIEW
Raquel Dos Santos, Ana Luísa Carvalho, A Cecília A Roque
The current chromatographic approaches used in protein purification are not keeping pace with the increasing biopharmaceutical market demand. With the upstream improvements, the bottleneck shifted towards the downstream process. New approaches rely in Anything But Chromatography methodologies and revisiting former techniques with a bioprocess perspective. Protein crystallization and precipitation methods are already implemented in the downstream process of diverse therapeutic biological macromolecules, overcoming the current chromatographic bottlenecks...
November 28, 2016: Biotechnology Advances
https://www.readbyqxmd.com/read/27906496/aerobic-expression-of-vitreoscilla-hemoglobin-improves-the-growth-performance-of-cho-k1-cells
#5
Mariana Juárez, Claudia H González-De la Rosa, Elisa Memún, Juan-Carlos Sigala, Alvaro R Lara
Inefficient carbon metabolism is a relevant issue during the culture of mammalian cells for the production of biopharmaceuticals. Therefore, cell engineering strategies to improve the metabolic and growth performance of cell lines are needed. The expression of Vitreoscilla stercoraria hemoglobin (VHb) has been shown to significantly reduce overflow metabolism and improve the aerobic growth of bacteria. However, the effects of VHb on mammalian cells have been rarely studied. Here, the impact of VHb on growth and lactate accumulation during CHO-K1 cell culture was investigated...
December 1, 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/27900054/scorpion-venoms-in-gastric-cancer
#6
Xiao-Ying Zhang, Pei-Ying Zhang
Venom secretions from snakes, scorpions, spiders and bees, have been widely applied in traditional medicine and current biopharmaceutical research. Possession of anticancer potential is another novel discovery for animal venoms and toxins. An increasing number of studies have shown the anticancer effects of venoms and toxins of snakes, and scorpions in vitro and in vivo, which were achieved mainly through the inhibition of cancer growth, arrest of cell cycle, induction of apoptosis and suppression of cancer metastasis...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898308/emerging-biopharmaceuticals-from-marine-actinobacteria
#7
REVIEW
Syed Shams Ul Hassan, Komal Anjum, Syed Qamar Abbas, Najeeb Akhter, Bibi Ibtesam Shagufta, Sayed Asmat Ali Shah, Umber Tasneem
Actinobacteria are quotidian microorganisms in the marine world, playing a crucial ecological role in the recycling of refractory biomaterials and producing novel secondary metabolites with pharmaceutical applications. Actinobacteria have been isolated from the huge area of marine organisms including sponges, tunicates, corals, mollusks, crabs, mangroves and seaweeds. Natural products investigation of the marine actinobacteria revealed that they can synthesize numerous natural products including alkaloids, polyketides, peptides, isoprenoids, phenazines, sterols, and others...
November 22, 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27893966/vaccination-via-chloroplast-genetics-affordable-protein-drugs-for-the-prevention-and-treatment-of-inherited-or-infectious-human-diseases
#8
Henry Daniell, Hui-Ting Chan, Elise K Pasoreck
Plastid-made biopharmaceuticals treat major metabolic or genetic disorders, including Alzheimer's, diabetes, hypertension, hemophilia, and retinopathy. Booster vaccines made in chloroplasts prevent global infectious diseases, such as tuberculosis, malaria, cholera, and polio, and biological threats, such as anthrax and plague. Recent advances in this field include commercial-scale production of human therapeutic proteins in FDA-approved cGMP facilities, development of tags to deliver protein drugs to targeted human cells or tissues, methods to deliver precise doses, and long-term stability of protein drugs at ambient temperature, maintaining their efficacy...
November 23, 2016: Annual Review of Genetics
https://www.readbyqxmd.com/read/27890772/integrative-analysis-of-dna-methylation-and-gene-expression-in-butyrate-treated-cho-cells
#9
Anna Wippermann, Oliver Rupp, Karina Brinkrolf, Raimund Hoffrogge, Thomas Noll
The cellular mechanisms responsible for the versatile properties of CHO cells as the major production cell line for biopharmaceutical molecules are not entirely understood yet, although several 'omics' data facilitate the understanding of CHO cells and their reactions to environmental conditions. However, genome-wide studies of epigenetic processes such as DNA methylation are still limited. To prove the applicability and usefulness of integrating DNA methylation and gene expression data in a biotechnological context, we exemplarily analyzed the time course of cellular reactions upon butyrate addition in antibody-producing CHO cells by whole-genome bisulfite sequencing and CHO-specific cDNA microarrays...
November 24, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27889071/using-x-ray-crystallography-to-simplify-and-accelerate-biologics-drug-development
#10
REVIEW
Mark L Brader, Edward N Baker, Michael F Dunn, Thomas M Laue, John F Carpenter
Every major biopharmaceutical company incorporates a protein crystallography unit that is central to its structure-based drug discovery efforts. Yet these capabilities are rarely leveraged toward the formal higher order structural characterization that is so challenging but integral to large-scale biologics manufacturing. Although the biotech industry laments the shortcomings of its favored biophysical techniques, x-ray crystallography is not even considered for drug development. Why not? We suggest that this is due, at least in part, to outdated thinking (for a recent industry-wide survey, see Gabrielson JP, Weiss IV WF...
November 23, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27885330/formulation-of-propolis-phenolic-acids-containing-microemulsions-and-their-biopharmaceutical-characterization
#11
Modestas Žilius, Kristina Ramanauskienė, Vaida Juškaitė, Vitalis Briedis
Microemulsions (MEs) were formulated using PEG-8 caprylic/capric glycerides and ethanolic propolis extracts. Characterization of MEs was performed by determining mean droplet size, polydispersity index, stability under varying external factors, and formulation effect on delivery of phenolic compounds into the skin ex vivo. Essential oils were included into the formulations of MEs and their influence on physical characteristics of the nanostructured systems as well as penetration into epidermis and dermis were evaluated...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27883886/cho-cells-can-make-more-protein
#12
Sarah W Harcum, Kelvin H Lee
A new comprehensive genome-scale metabolic model of Chinese hamster ovary cells identifies pathways for improving biopharmaceutical protein production.
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27871727/critical-material-attributes-of-strip-films-loaded-with-poorly-water-soluble-drug-nanoparticles-ii-impact-of-polymer-molecular-weight
#13
Scott M Krull, Jennifer Ammirata, Sonia Bawa, Meng Li, Ecevit Bilgili, Rajesh N Davé
Recent work established polymer strip films as a robust platform for delivery of poorly water-soluble drug particles. However, a simple means of manipulating rate of drug release from films with minimal impact on film mechanical properties has yet to be demonstrated. This study explores the impact of film-forming polymer molecular weight (MW) and concentration on properties of polymer films loaded with poorly water-soluble drug nanoparticles. Nanoparticles of griseofulvin, a model Biopharmaceutics Classification System class II drug, were prepared in aqueous suspension via wet stirred media milling...
November 18, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27869296/segmented-linear-modeling-of-cho-fed-batch-culture-and-its-application-to-large-scale-production
#14
Bassem Ben Yahia, Boris Gourevitch, Laetitia Malphettes, Elmar Heinzle
We describe a systematic approach to model CHO metabolism during biopharmaceutical production across a wide range of cell culture conditions. To this end, we applied the metabolic steady state concept. We analyzed and modeled the production rates of metabolites as a function of the specific growth rate. First, the total number of metabolic steady state phases and the location of the breakpoints were determined by recursive partitioning. For this, the smoothed derivative of the metabolic rates with respect to the growth rate were used followed by hierarchical clustering of the obtained partition...
November 7, 2016: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27869291/managing-innovation-to-maximize-value-along-the-discovery-translation-application-continuum
#15
S A Waldman, A Terzic
Success in pharmaceutical development led to a record 51 drugs approved in the past year, surpassing every previous year since 1950. Technology innovation enabled identification and exploitation of increasingly precise disease targets ensuring next generation diagnostic and therapeutic products for patient management. The expanding biopharmaceutical portfolio stands, however, in contradistinction to the unsustainable costs that reflect remarkable challenges of clinical development programs. This annual Therapeutic Innovations issue juxtaposes advances in translating molecular breakthroughs into transformative therapies with essential considerations for lowering attrition and improving the cost-effectiveness of the drug-development paradigm...
November 21, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27865856/melatonin-loaded-silica-coated-with-hydroxypropyl-methylcellulose-phthalate-for-enhanced-oral-bioavailability-preparation-and-in-vitro-in-vivo-evaluation
#16
Yuanyuan Li, Xiuhua Zhao, Yuangang Zu, Lingling Wang, Weiwei Wu, Yiping Deng, Chang Zu, Yanjie Liu
Melatonin (MLT) is a small molecule with low water solubility and high permeability. According to the Biopharmaceutics Classification System, MLT is a class II drug exhibiting a very short half-life and minimal and variable bioavailability. This work aimed to establish a delivery system composed of an enteric MLT nanosphere with favorably controlled and sustained release characteristics superior to those of raw MLT. The nanosphere was composed of hydroxypropyl methylcellulose phthalate (HP55) and silica (SiO2) with MLT...
November 17, 2016: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/27863666/nasal-powders-of-thalidomide-for-local-treatment-of-nose-bleeding-in-persons-affected-by-hereditary-hemorrhagic-telangiectasia
#17
G Colombo, F Bortolotti, V Chiapponi, F Buttini, F Sonvico, R Invernizzi, F Quaglia, C Danesino, F Pagella, P Russo, R Bettini, P Colombo, A Rossi
In this work nasal powder formulations of thalidomide were designed and studied to be used by persons affected by hereditary hemorrhagic telangiectasia as a complementary anti-epistaxis therapy, with the goal of sustaining the effect obtained with thalidomide oral treatment after its discontinuation for adverse effects. Three nasal powders were prepared using as carriers β-CD or its more hydrophilic derivatives such as hydropropyl-β-CD and sulphobutylether-β-CD and tested with respect to technological and biopharmaceutical features after emission with active and passive nasal powder devices...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27863308/in-vitro-biopharmaceutical-evaluation-of-ciprofloxacin-metal-cation-complexes-for-pulmonary-administration
#18
J Brillault, F Tewes, W Couet, J C Olivier
Pulmonary delivery of fluoroquinolones (FQs) is an interesting approach to treat lung infections as it may lead to high local concentrations while minimizing systemic exposure. However, FQs have a rapid diffusion through the lung epithelium giving the pulmonary route no advantage compared to the oral route. Interactions between FQs and metal cations form complexes which limit the diffusion through the epithelial barrier and would reduce the absorption of FQs and maintain high concentrations in the lung. The effects of this complexation depend on the FQ and the metal cations and optimum partners should be selected through in vitro experiments prior to aerosol drug formulation...
November 15, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27863173/heterologous-expression-and-purification-of-active-l-asparaginase-i-of-saccharomyces-cerevisiae-in-escherichia-coli-host
#19
João H P M Santos, Iris M Costa, João V D Molino, Mariana S M Leite, Marcela V Pimenta, João A P Coutinho, Adalberto Pessoa, Sónia P M Ventura, André M Lopes, Gisele Monteiro
L-asparaginase (ASNase) is a biopharmaceutical widely used to treat child leukemia. However, it presents some side effects, and in order to provide an alternative biopharmaceutical, in this work, the genes encoding ASNase from Saccharomyces cerevisiae (Sc_ASNaseI and Sc_ASNaseII) were cloned in the prokaryotic expression system Escherichia coli. In the 93 different expression conditions tested, the Sc_ASNaseII protein was always obtained as an insoluble and inactive form. However, the Sc_ASNaseI (His)6 -tagged recombinant protein was produced in large amounts in the soluble fraction of the protein extract...
November 14, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27856232/improved-recombinant-antibody-production-by-cho-cells-using-a-production-enhancer-dna-element-with-repeated-transgene-integration-at-a-predetermined-chromosomal-site
#20
Yoshinori Kawabe, Takanori Inao, Shodai Komatsu, Guan Huang, Akira Ito, Takeshi Omasa, Masamichi Kamihira
Chinese hamster ovary (CHO) cells are one of the most useful host cell lines for the production of biopharmaceutical proteins. Although a series of production processes have been refined to improve protein productivity and cost performance, establishing producer cells is still time-consuming and labor-intensive. Recombinase-mediated site-specific gene integration into a predetermined chromosomal locus may enable predictable protein expression, reducing the laborious process of cell screening. We previously developed an accumulative site-specific gene integration system (AGIS) using Cre recombinase and mutated loxP sites for transgene integration and amplification in the CHO cell genome...
November 14, 2016: Journal of Bioscience and Bioengineering
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