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1.
Protein Solvent Interaction: Transition of Protein-solvent Interaction Concept from Basic Research into Solvent Manipulation of Chromatography.
Arakawa, T, Kita, Y
Current protein & peptide science. 2019;(1):34-39
Abstract
Previously, we have reviewed in this journal (Arakawa, T., Kita, Y., Curr. Protein Pept. Sci., 15, 608-620, 2014) the interaction of arginine with proteins and various applications of this solvent additive in the area of protein formulations and downstream processes. In this special issue, we expand the concept of protein-solvent interaction into the analysis of the effects of solvent additives on various column chromatography, including mixed-mode chromatography. Earlier in our research, we have studied the interactions of such a variety of solvent additives as sugars, salts, amino acids, polymers and organic solvents with a variety of proteins, which resulted in mechanistic understanding on their protein stabilization and precipitation effects, the latter known as Hofmeister series. While such a study was then a pure academic research, rapid development of genetic engineering technologies and resultant biotechnologies made it a valuable knowledge in fully utilizing solvent additives in manipulation of protein solution, including column chromatography.
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2.
Solvent Composition Effects on the Structural Properties of the Aβ42 Monomer from the 3D-RISM-KH Molecular Theory of Solvation.
Blinov, N, Wishart, DS, Kovalenko, A
The journal of physical chemistry. B. 2019;(11):2491-2506
Abstract
Structural characterization of amyloid (A)β peptides implicated in Alzheimer's disease is a challenging problem due to their intrinsically disordered nature and their high propensity for aggregation. Only limited information is currently available from experiments on conformational properties and aggregation pathways of the peptides in cellular environments. In silico modeling complements experimental information, providing atomistic insight into structure and dynamics of different Aβ species. All-atom explicit solvent molecular dynamics (MD) simulations with a properly selected force field can deliver reliable structural and dynamic information. In the case of intrinsically disordered Aβ peptides, enhanced sampling simulations beyond the nanosecond time scale are required to obtain statistically meaningful results even for simple solvent conditions. To overcome the challenges of conformational sampling in crowded cellular environments, alternative approaches have to be used, including postprocessing of MD data. In this study, we employ the statistical-mechanical, three-dimensional reference interaction site model with the Kovalenko-Hirata closure integral equation molecular theory of solvation to describe solvent composition effects on the conformational equilibrium in a structural ensemble of the Aβ42 (covering residues 1-42) monomer based on a statistical reweighting technique. The methodology enables a computationally efficient prediction on how different factors in the cellular environment, such as solvent composition, nonpolar solvation, and macromolecular crowding, affect the structural properties of the monomer. Similarities have been identified between changes in the structural ensemble caused by nonpolar solvation and crowded environments modeled by ionic solution with large negative ions. In particular, both solvent conditions reduce the random coil content and enhance the helical structure content of the monomer. In contrast to the previous studies, which reported increased α-helical content of peptides in crowded environments, this work attributes these structural features to the difference in solvent exposure of hydrophilic residues of the monomer for different secondary structure elements, rather than to (entropic) excluded volume effects.
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3.
Four types of human platelet lysate, including one virally inactivated by solvent-detergent, can be used to propagate Wharton jelly mesenchymal stromal cells.
Chen, MS, Wang, TJ, Lin, HC, Burnouf, T
New biotechnology. 2019;:151-160
Abstract
There is accumulating experimental evidence that human platelet lysate (HPL) made from platelet concentrates can replace fetal bovine serum (FBS) as a xeno-free clinical-grade supplement of growth media to expand mesenchymal stromal cells (MSCs). However, uncertainties exist in regard to impacts that various manufacturing methods of HPL can exert on the expansion and differentiation capacity of MSCs. In particular, there is a need to evaluate the possibility of implementing virus-inactivation treatment during HPL production to ensure optimal safety of industrial HPL pools. Expired human platelet concentrates from four different donors were pooled and subjected to freeze-thaw cycles (-80/+37 °C), followed or not by serum-conversion by calcium chloride, heat-treatment at 56 °C for 30 min, or solvent-detergent (S/D) virus inactivation. The concentrations of total proteins, growth factors and fibrinogen, and the chemical compositions of the HPLs were characterized. The impact of HPL supplementation on the cell morphology, doubling time, immunophenotype and trilineage differentiation capacity of Wharton jelly MSCs (WJMSCs) were compared over five passages, using FBS as a control and normalizing the protein content. Data showed that WJMSCs expanded equally well, exhibited a typical fibroblast morphology, had short doubling times, maintained their immunophenotypes, and differentiated into chondrocyte, osteocyte, and adipocyte lineages in all HPL-supplemented media, all of which were more effective than FBS. In conclusion, we found minimal detectable impact of the HPL manufacturing process, including S/D virus inactivation, on the suitability of expanding WJMSCs in vitro.
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4.
Fast NMR method to probe solvent accessibility and disordered regions in proteins.
Faustino, AF, Barbosa, GM, Silva, M, Castanho, MARB, Da Poian, AT, Cabrita, EJ, Santos, NC, Almeida, FCL, Martins, IC
Scientific reports. 2019;(1):1647
Abstract
Understanding protein structure and dynamics, which govern key cellular processes, is crucial for basic and applied research. Intrinsically disordered protein (IDP) regions display multifunctionality via alternative transient conformations, being key players in disease mechanisms. IDP regions are abundant, namely in small viruses, allowing a large number of functions out of a small proteome. The relation between protein function and structure is thus now seen from a different perspective: as IDP regions enable transient structural arrangements, each conformer can play different roles within the cell. However, as IDP regions are hard and time-consuming to study via classical techniques (optimized for globular proteins with unique conformations), new methods are required. Here, employing the dengue virus (DENV) capsid (C) protein and the immunoglobulin-binding domain of streptococcal protein G, we describe a straightforward NMR method to differentiate the solvent accessibility of single amino acid N-H groups in structured and IDP regions. We also gain insights into DENV C flexible fold region biological activity. The method, based on minimal pH changes, uses the well-established 1H-15N HSQC pulse sequence and is easily implementable in current protein NMR routines. The data generated are simple to interpret, with this rapid approach being an useful first-choice IDPs characterization method.
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5.
Solid dispersion technology as a strategy to improve the bioavailability of poorly soluble drugs.
Cid, AG, Simonazzi, A, Palma, SD, Bermúdez, JM
Therapeutic delivery. 2019;(6):363-382
Abstract
Over the last half-century, solid dispersions (SDs) have been intensively investigated as a strategy to improve drugs solubility and dissolution rate, enhancing oral bioavailability. In this review, an overview of the state of the art of SDs technology is presented, focusing on their classification, the main preparation methods, the limitations associated with their instability, and the marketed products. To fully take advantage of SDs potential, an improvement in their physical stability and the ability to prolong the supersaturation of the drug in gastrointestinal fluids is required, as well as a better scientific understanding of scale-up for defining a robust manufacturing process. Taking these limitations into account will contribute to increase the number of marketed pharmaceutical products based on SD technology.
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6.
Thermodynamic of solvation, solute - Solvent electron transfer and ionization potential of BSCAPE molecule and its UV-vis spectra in aqueous solution.
Holtomo, O, Nsangou, M, Fifen, JJ, Motapon, O
Journal of molecular graphics & modelling. 2019;:100-111
Abstract
The molecular system 2-Phenylethyl (2E)-3-(1-benzenesulfonyl-4,5-dihydroxyphenyl) acrylate (BSCAPE) is a phenolic acid that covers a large spectrum of biological properties. The investigations of solvation and oxidation processes of BSCAPE molecule by computational means were the challenge of this present work. Water was required for solvation throughout the work. The explicit H2O were sequentially added to form the complexes BSCAPE(H2O)n=0-11. The discrete - continuum model was at the heart of this work. DFT and TD-DFT both associated to the continuum model SMD were required. Hence, the structures, the solvation energies, the energies of solute - solvent electron transfer (SSET), the ionisation potential (IP), and the UV-vis spectra were studied. It comes out that, the structure of the CAPE part included in BSCAPE agrees well with the available experimental values of CAPE but with a minor influence due to the presence of benzensulfonyl group. The enthalpy and free energy of solvation increase linearly with nH2O. The global reactivity indexes were assessed to appreciate the oxidation of BSCAPE. The latter quality was strongly assessed by the enthalpy and free energy of SSET and IP. The SSET potential increase with nH2O and the size of water clusters. The values 723.16 and 711.62 kJ/mol were found for enthalpy and free energy of IP respectively. Then in aqueous solution, the results fall down and upon addition of nH2O, they approach gas phase value for 11H2O and still are not stabilized. Therefore, the resistance to oxidation starts to raise at this level. Elsewhere, the UV-vis spectra of BSCAPE present four important peaks about 279.3, 234.8, 208.4 and 199.4 nm in gaseous state. The excitation shifts to the red as the number of H2O increase. Their oscillator strengths also increase with solvation.
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7.
The effect of adolescent inhalant abuse on energy balance and growth.
Crossin, R, Qama, A, Andrews, ZB, Lawrence, AJ, Duncan, JR
Pharmacology research & perspectives. 2019;(4):e00498
Abstract
The abuse of volatile solvents such as toluene is a significant public health concern, predominantly affecting adolescents. To date, inhalant abuse research has primarily focused on the central nervous system; however, inhalants also exert effects on other organ systems and processes, including metabolic function and energy balance. Adolescent inhalant abuse is characterized by a negative energy balance phenotype, with the peak period of abuse overlapping with the adolescent growth spurt. There are multiple components within the central and peripheral regulation of energy balance that may be affected by adolescent inhalant abuse, such as impaired metabolic signaling, decreased food intake, altered dietary preferences, disrupted glucose tolerance and insulin release, reduced adiposity and skeletal density, and adrenal hypertrophy. These effects may persist into abstinence and adulthood, and the long-term consequences of inhalant-induced metabolic dysfunction are currently unknown. The signs and symptoms resulting from chronic adolescent inhalant abuse may result in a propensity for the development of adult-onset metabolic disorders such as type 2 diabetes, however, further research investigating the long-term effects of inhalant abuse upon energy balance and metabolism are needed. This review addresses several aspects of the short- and long-term effects of inhalant abuse relating to energy and metabolic processes, including energy balance, intake and expenditure; dietary preferences and glycemic control; and the dysfunction of metabolic homeostasis through altered adipose tissue, bone, and hypothalamic-pituitary-adrenal axis function.
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8.
Does nab-paclitaxel have a higher incidence of peripheral neuropathy than solvent-based paclitaxel? Evidence from a systematic review and meta-analysis.
Guo, X, Sun, H, Dong, J, Feng, Y, Li, H, Zhuang, R, Wang, P, Cai, W, Zhou, Y
Critical reviews in oncology/hematology. 2019;:16-23
Abstract
Paclitaxel-induced peripheral neuropathy is a common reason for dose reduction or early cessation of therapy. Nab-paclitaxel was developed to provide additional clinical benefits and overcome the safety drawbacks of solvent-based paclitaxel. However, the incidence of peripheral neuropathy induced by nab-paclitaxel was reported higher than solvent-based paclitaxel but evidence remains inconsistent. Therefore, we conducted a meta-analysis to compare the incidence and severity of peripheral neuropathy between nab-paclitaxel and solvent-based paclitaxel mono-chemotherapy. In total, 24 articles were included in this meta-analysis. Results revealed the incidence of peripheral neuropathy induced by nab-paclitaxel was higher than solvent-based paclitaxel. The dosage and assessment method could influence the comparison of the incidence and severity of peripheral neuropathy between nab-paclitaxel and solvent-based paclitaxel. Current evidence suggests the incidence of peripheral neuropathy induced by nab-paclitaxel was higher than solvent-based paclitaxel among cancer patients received mono-chemotherapy. When received nab-paclitaxel, more attention should be paid to peripheral neuropathy.
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9.
Environmental and Genetic Factors Influencing Kidney Toxicity.
Lash, LH
Seminars in nephrology. 2019;(2):132-140
Abstract
The kidneys are a frequent target organ for toxicity from exposures to various environmental chemicals and agents. To understand the risk to human health from such exposures, it is important to consider both the underlying chemical and pathologic mechanisms and factors that may modify susceptibility to injury. Choices of exemplary environmental agents to review are based on those with selective effects on the kidneys and for which significant amounts of mechanistic and human data are available. These include the heavy metals cadmium and arsenic, fluoride, the organic solvents trichloroethylene and perchloroethylene, drinking water disinfection by-products haloacids, food and herbal drug contaminants aristolochic acid and melamine, and heat stress. Some common mechanistic features of all these diverse exposures are highlighted, and include oxidative stress and mitochondrial damage. Two major genetic factors that are discussed include genetic polymorphisms in plasma membrane transporters that catalyze uptake and accumulation or efflux and elimination of environmental chemicals, and genetic polymorphisms in bioactivation enzymes that generate toxic and reactive metabolites. Identification of methods to prevent environmental toxicant-associated kidney damage and understanding the genetic factors that influence kidney function and the kidney's response to exposures can be applied to refine risk assessments.
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10.
Chemical treatments for modification and immobilization to improve the solvent-stability of lipase.
Matsumoto, T, Yamada, R, Ogino, H
World journal of microbiology & biotechnology. 2019;(12):193
Abstract
Lipase is a lipolytic enzyme that catalyzes the hydrolysis of lipids and esterification reactions. Lipase has been utilized in industrial uses, food processing, and therapeutic applications as a biocatalyst. However, substrates of lipase are often insoluble in water, and this problem limits its utility. Lipases are also used in organic solvents where the solvent-stability of lipase is an important factor. There is a huge number of approaches that can be undertaken to improve the organic solvent-stability of lipases. For example, screening of solvent-tolerant lipase in nature and direct evolution of lipase using genetic engineering are some of the employed approaches. Here, we focus on approaches based on the chemical treatment of lipases for modification and immobilization. The solvent-stability of lipase was improved by the attachment of other molecules, such as surfactants, polymers, and carbohydrates. The immobilization of the enzyme is been known to be an effective approach for not only recycling the enzyme but also its stabilization. Several reports have demonstrated that the solvent-stability of lipase is also improved by immobilization. In this review, we provide an overview of the approaches used to improve the solvent-stability of lipase.