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1.
Revisiting the Self-Assembly of Highly Aromatic Phenylalanine Homopeptides.
Mayans, E, Alemán, C
Molecules (Basel, Switzerland). 2020;(24)
Abstract
Diphenylalanine peptide (FF), which self-assembles into rigid tubular nanostructures, is a very short core recognition motif in Alzheimer's disease β-amyloid (Aβ) polypeptide. Moreover, the ability of the phenylalanine (F or Phe)-homopeptides to self-assemble into ordered nanostructures has been proved. Within this context it was shown that the assembly preferences of this family of compounds is altered by capping both the N- and C-termini using highly aromatic fluorenyl groups (i.e., fluorenyl-9-methoxycarbonyl and 9-fluorenylmethyl ester, named Fmoc and OFm, respectively). In this article the work performed in the field of the effect of the structure and incubation conditions on the morphology and polymorphism of short (from two to four amino acid residues) Phe-homopeptides is reviewed and accompanied by introducing some new results for completing the comparison. Special attention has been paid to the influence of solvent: co-solvent mixture used to solubilize the peptide, the peptide concentration and, in some cases, the temperature. More specifically, uncapped (FF, FFF, and FFFF), N-capped with Fmoc (Fmoc-FF, Fmoc-FFF, and Fmoc-FFFF), C-capped with OFm (FF-OFm), and doubly capped (Fmoc-FF-OFm, Fmoc-FFF-OFm, and Fmoc-FFFF-OFm) Phe-homopeptides have been re-measured. Although many of the experienced assembly conditions have been only revisited as they were previously reported, other experimental conditions have been examined by the first time in this work. In any case, pooling the effect of highly aromatic blocking groups in a single study, using a wide variety of experimental conditions, allows a perspective of how the disappearance of head-to-tail electrostatic interactions and the gradual increase in the amount of π-π stacking interactions, affects the morphology of the assemblies. Future technological applications of Phe-homopeptides can be envisaged by choosing the most appropriate self-assemble structure, defining not only the length of the peptide but also the amount and the position of fluorenyl capping groups.
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2.
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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3.
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.
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4.
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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5.
Generalized Born Implicit Solvent Models for Biomolecules.
Onufriev, AV, Case, DA
Annual review of biophysics. 2019;:275-296
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Abstract
It would often be useful in computer simulations to use an implicit description of solvation effects, instead of explicitly representing the individual solvent molecules. Continuum dielectric models often work well in describing the thermodynamic aspects of aqueous solvation and can be very efficient compared to the explicit treatment of the solvent. Here, we review a particular class of so-called fast implicit solvent models, generalized Born (GB) models, which are widely used for molecular dynamics (MD) simulations of proteins and nucleic acids. These approaches model hydration effects and provide solvent-dependent forces with efficiencies comparable to molecular-mechanics calculations on the solute alone; as such, they can be incorporated into MD or other conformational searching strategies in a straightforward manner. The foundations of the GB model are reviewed, followed by examples of newer, emerging models and examples of important applications. We discuss their strengths and weaknesses, both for fidelity to the underlying continuum model and for the ability to replace explicit consideration of solvent molecules in macromolecular simulations.
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6.
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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7.
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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8.
The solvent side of proteinaceous membrane-less organelles in light of aqueous two-phase systems.
Zaslavsky, BY, Ferreira, LA, Darling, AL, Uversky, VN
International journal of biological macromolecules. 2018;:1224-1251
Abstract
Water represents a common denominator for liquid-liquid phase transitions leading to the formation of the polymer-based aqueous two-phase systems (ATPSs) and a set of the proteinaceous membrane-less organelles (PMLOs). ATPSs have a broad range of biotechnological applications, whereas PMLOs play a number of crucial roles in cellular compartmentalization and often represent a cellular response to the stress. Since ATPSs and PMLOs contain high concentrations of polymers (such as polyethylene glycol (PEG), polypropylene glycol (PPG), Ucon, and polyvinylpyrrolidone (PVP), Dextran, or Ficoll) or biopolymers (peptides, proteins and nucleic acids), it is expected that the separated phases of these systems are characterized by the noticeable changes in the solvent properties of water. These changes in solvent properties can drive partitioning of various compounds (proteins, nucleic acids, organic low-molecular weight molecules, metal ions, etc.) between the phases of ATPSs or between the PMLOs and their surroundings. Although there is a sizable literature on the properties of the ATPS phases, much less is currently known about PMLOs. In this perspective article, we first represent liquid-liquid phase transitions in water, discuss different types of biphasic (or multiphasic) systems in water, and introduce various PMLOs and some of their properties. Then, some basic characteristics of polymer-based ATPSs are presented, with the major focus being on the current understanding of various properties of ATPS phases and solvent properties of water inside them. Finally, similarities and differences between the polymer-based ATPSs and biological PMLOs are discussed.
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9.
Effect of Organic Solvents on Microalgae Growth, Metabolism and Industrial Bioproduct Extraction: A Review.
Miazek, K, Kratky, L, Sulc, R, Jirout, T, Aguedo, M, Richel, A, Goffin, D
International journal of molecular sciences. 2017;(7)
Abstract
In this review, the effect of organic solvents on microalgae cultures from molecular to industrial scale is presented. Traditional organic solvents and solvents of new generation-ionic liquids (ILs), are considered. Alterations in microalgal cell metabolism and synthesis of target products (pigments, proteins, lipids), as a result of exposure to organic solvents, are summarized. Applications of organic solvents as a carbon source for microalgal growth and production of target molecules are discussed. Possible implementation of various industrial effluents containing organic solvents into microalgal cultivation media, is evaluated. The effect of organic solvents on extraction of target compounds from microalgae is also considered. Techniques for lipid and carotenoid extraction from viable microalgal biomass (milking methods) and dead microalgal biomass (classical methods) are depicted. Moreover, the economic survey of lipid and carotenoid extraction from microalgae biomass, by means of different techniques and solvents, is conducted.
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10.
Enthalpy-entropy compensation: the role of solvation.
Dragan, AI, Read, CM, Crane-Robinson, C
European biophysics journal : EBJ. 2017;(4):301-308
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Abstract
Structural modifications to interacting systems frequently lead to changes in both the enthalpy (heat) and entropy of the process that compensate each other, so that the Gibbs free energy is little changed: a major barrier to the development of lead compounds in drug discovery. The conventional explanation for such enthalpy-entropy compensation (EEC) is that tighter contacts lead to a more negative enthalpy but increased molecular constraints, i.e., a compensating conformational entropy reduction. Changes in solvation can also contribute to EEC but this contribution is infrequently discussed. We review long-established and recent cases of EEC and conclude that the large fluctuations in enthalpy and entropy observed are too great to be a result of only conformational changes and must result, to a considerable degree, from variations in the amounts of water immobilized or released on forming complexes. Two systems exhibiting EEC show a correlation between calorimetric entropies and local mobilities, interpreted to mean conformational control of the binding entropy/free energy. However, a substantial contribution from solvation gives the same effect, as a consequence of a structural link between the amount of bound water and the protein flexibility. Only by assuming substantial changes in solvation-an intrinsically compensatory process-can a more complete understanding of EEC be obtained. Faced with such large, and compensating, changes in the enthalpies and entropies of binding, the best approach to engineering elevated affinities must be through the addition of ionic links, as they generate increased entropy without affecting the enthalpy.