Future Strategies for Commercial Biocatalysis
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Today, biocatalysis is synonymous with so much more than just one isolated enzymatic reaction in a chemical synthesis (Sheldon and Woodley, 2018). One-pot, multistep, chemoenzymatic cascades, cell-free and cell-based biocatalytic cascades are the new frontier. These cascades lead to process intensification by minimising the isolation of intermediates and decreasing unit operations, which has a direct impact on waste reduction and lowering costs. Despite the increased complexity of multistep cascades, technological advances in enzyme discovery, bioinformatics and protein engineering have enabled their increasingly rapid and efficient development. This shift has been matched by the rapid development in chemo-catalysis of water-compatible organo- and transition metal catalysts that facilitates ready incorporation of chemo-catalysis with enzymes into chemoenzymatic cascades.
Design of Bioresponsive Polymers
Deepa H. Patel in Bioresponsive Polymers, 2020
An aptitude of the glucose-responsive hydrogel systems has to present self-regulated insulin release in reaction to blood glucose level, in this manner concentration of insulin controlled within a normal range [104]. The most familiar characteristics of this hydrogel system make use of biocatalysts or else immobilized enzymes, distinctively GOx [105–107]. When an enzyme is covalently joined to a smart polymer, environmental alterations bring about major alterations in the conformation of polymer which drastically influences the activity of enzyme along with substrate contact to the enzyme molecule, which is a common mechanism behind this. These biocatalysts take action as a result of catalyzing an enzymatic reaction in their soluble state furthermore the products of this enzymatic reaction followed by activates the gel’s phase transition. Investigations have revealed that gel beads of the enzyme-biopolymer complex produced by conjugating the biopolymer CS with carbodiimide conjugation [105]. GOx develops the pH sensitivity of the polymer used to immobilize the enzyme for the delivery of insulin (see Figure 2.3) [108]. For the formation of gluconic acid, GOx oxidizes glucose which brings about a pH alter in the surroundings [48]. Volume transition has been established by the pH-sensitive hydrogel responding to the lower pH, which happens as a result of the formation of gluconic acid. Consequently, the body’s glucose concentrations control the swelling ratio of the hydrogel [49].
In Vitro to In Vivo Extrapolation of Metabolic Rate Constants for Physiologically Based Pharmacokinetic Models
John C. Lipscomb, Edward V. Ohanian in Toxicokinetics and Risk Assessment, 2016
Some enzymes are membrane bound to cellular organelles, such as the endoplasmic reticulum or mitochondria, while others are present in the soluble portion of the cell known as the cytoplasm. However, the aqueous cytoplasm of the cell is highly organized via a group of polymeric proteins called the cytomatrix, and soluble enzymes appear to be associated with this dynamic network (3–5). This intracellular organization can influence the efficiency of enzyme catalysis and promote the coupling of metabolic processes. For example, a chemical that is hydroxylated by endoplasmic reticulum-bound cytochrome P450 (CYP) can be so efficiently conjugated with glucuronic acid by neighboring membrane-bound glucuronosyl transferase that the free alcohol product cannot be detected in the cell. The coupling of metabolic processes can lead to very efficient detoxication of toxicants, but it can also promote toxication processes that can ultimately lead to cellular damage and death.
Glycoconjugate vaccines: current approaches towards faster vaccine design
Published in Expert Review of Vaccines, 2019
Francesca Micoli, Linda Del Bino, Renzo Alfini, Filippo Carboni, Maria Rosaria Romano, Roberto Adamo
Modern synthetic techniques are, therefore, becoming powerful tools to accelerate identification of carbohydrate antigens without the need for polysaccharide purification from the biological matrix. Enzyme-catalyzed oligosaccharide assembly is an interesting alternative to chemical synthesis of complex bacterial glycans, since the enzymatic glycosylation by glycosyltransferases allows stereo- and regio-selectivity, without the need to undergo tedious protecting group manipulations. The enzymatic reactions can take place in aqueous solutions, and require only limited control of reaction conditions (such as temperature, system pH, and, in certain cases, metal catalysis). Also, since no toxic byproducts are being generated in this glycosylation process, enzymatic synthesis of oligosaccharides can be considered environmentally friendly [73]. These advantages make enzyme-based carbohydrate production highly attractive for industrialization. However, despite being conceptually possible, the automated enzymatic synthesis is not yet fully available [73] (Figure 1(d,e)).
Quetiapine and novel PDE10A inhibitors potentiate the anti-BuChE activity of donepezil
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Joanna Sikora, Maria Podsiedlik, Tadeusz Pietras, Marcin Kosmalski, Mikołaj Matłoka, Rafał Moszczyński-Petkowski, Maciej Wieczorek, Magdalena Markowicz-Piasecka
The effects of quetiapine, CPL500036-01 and CPL500036-02 on the activity of both ChEs were determined according to Ellman with modifications22,23. Briefly, the experiments were conducted on a CE 2021 spectrophotometer (CECIL Cambridge, UK) with circulating thermostated water (37 °C) and a Model 300 Electronic Stirrer (Rank Brothers Ltd, England). The biological sample, consisting of a 400-fold diluted solution of haemolysed erythrocytes or 200-fold diluted plasma was incubated for 15 min (37 °C) with DTNB; the tested compound was then added in a volume of 10 µL. The enzymatic reaction was initiated by addition of a reaction substrate (ATC or BTC). The absorbance was continuously recorded at λ = 436 nm for three minutes, and the maximal velocity of the reaction was counted on the basis of changes in absorbance over time.
Recent advances in the development of polyethylenimine-based gene vectors for safe and efficient gene delivery
Published in Expert Opinion on Drug Delivery, 2019
Cuiping Jiang, Jiatong Chen, Zhuoting Li, Zitong Wang, Wenli Zhang, Jianping Liu
As the substances that are inherently present in the human body, biological molecules draw growing interests as promising triggering motifs in the design of smart PEI-based gene vectors. Among different classes of biological components, ATP, enzyme, glucose, and antigen are the most attractive endogenous stimuli that enable biomolecule-responsive release. As we all know, enzymes are potent catalysts during almost all biological processes, and enzyme catalysis is highly selective towards specific substrates under mild conditions. Using tumor as an example again, several enzymes (i.e. proteases, lipase, hyaluronidase (HAase), etc.) have great potential to be specific stimuli in a controlled gene delivery system [117]. For instance, Yin et al. [118] reported an HA-conjugated PEI polymer for the active tumor targeting via interaction of HA with CD44 receptor. Once the nanocarrier reached the tumor extracellular matrix, the surface layer of HA would be deshielded under the catalysis of HAase, leading to the enhanced cellular uptake owing to the exposure of positive charges.
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