Site-Specific PEGylation of Therapeutic Proteins

The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as well as increasing the cost of therapy. One of the main strategies to alleviate these problems is to link a polyethylene glycol (PEG) group to the protein of interest. This process, called PEGylation, has grown dramatically in recent years resulting in several approved drugs. Installing a single PEG chain at a defined site in a protein is challenging. Recently, there is has been considerable research into various methods for the site-specific PEGylation of proteins. This review seeks to summarize that work and provide background and context for how site-specific PEGylation is performed. After introducing the topic of site-specific PEGylation, recent developments using chemical methods are described. That is followed by a more extensive discussion of bioorthogonal reactions and enzymatic labeling.     

Catalytic Hydrocracking of a Bitumen‐Derived Asphaltene over NiMo/γ‐Al2O3 at Various Temperatures

Hydrocracking of a bitumen‐derived asphaltene over NiMo/γ‐Al₂O₃ was investigated in a microbatch reactor at varying temperatures. The molar kinetics of asphaltene cracking reaction was examined by fitting the experimental data. Below a defined temperature, the molar reaction showed the first‐order kinetic feature while at higher temperatures secondary reactions such as coke formation became significant, causing deviation of the reaction behavior from the proposed first‐order kinetic model. Selectivity analysis proved that dominant products varied from gases to liquids to gases with increasing temperature, shifting the dominant reaction from C–S bonds cleavage to C–C bonds cleavage.     

Fold and flexibility: what can proteins' mechanical properties tell us about their folding nucleus?

The determination of a protein''s folding nucleus, i.e. a set of native contacts playing an important role during its folding process, remains an elusive yet essential problem in biochemistry. In this work, we investigate the mechanical properties of 70 protein structures belonging to 14 protein families presenting various folds using coarse-grain Brownian dynamics simulations. The resulting rigidity profiles combined with multiple sequence alignments show that a limited set of rigid residues, which we call the consensus nucleus, occupy conserved positions along the protein sequence. These residues'' side chains form a tight interaction network within the protein''s core, thus making our consensus nuclei potential folding nuclei. A review of experimental and theoretical literature shows that most (above 80%) of these residues were indeed identified as folding nucleus member in earlier studies.     

Low cycle fatigue behavior of a eutectic 80Au/20Sn solder alloy

The eutectic 80Au/20Sn solder alloy is widely used in high power electronics and optoelectronics packaging. In this study, low cycle fatigue behavior of a eutectic 80Au/20Sn solder alloy is reported. The 80Au/20Sn solder shows a quasi-static fracture characteristic at high strain rates, and then gradually transforms from a transgranular fracture (dominated by fatigue damage) to intergranular fracture (dominated by creep damage) at low strain rates with increasing temperature. Coffin-Manson and Morrow models are proposed to evaluate the low cycle fatigue behavior of the 80Au/20Sn solder. Besides, the 80Au/20Sn solder has enhanced fatigue resistance compared to the 63Sn/37Pb solder.     

Structures and properties of chicken myofibrillar protein gel induced by microwave heating

Structures and properties of myofibrillar protein gel prepared at different power (300–800 W) were evaluated. Amino acid analysis demonstrated that changes in microwave power did not alter primary structure of gel. However, an increase in microwave power could change higher structures of gel. As microwave power increased, α-helix content decreased and β-sheet content increased. Increased microwave power probably facilitated protein to unfold and expose the internal groups, causing surface hydrophobicity and the formation of disulphide bonds were enhanced, which indicated changes in tertiary and quaternary structures of protein. At 500 W, gel had the best ultrastructure where surface morphology, springiness and water holding capacity reached the optimum. Our findings suggested that microwave at an appropriate power (500 W) could change higher structures of myofibrillar protein gel to achieve desired processing and quality protein gel characteristics.     

Physical Stability of Octenyl Succinate–Modified Polysaccharides and Whey Proteins for Potential Use as Bioactive Carriers in Food Systems

The high cost and potential toxicity of biodegradable polymers like poly(lactic‐co‐glycolic)acid (PLGA) has increased the interest in natural and modified biopolymers as bioactive carriers. This study characterized the physical stability (water sorption and state transition behavior) of selected starch and proteins: octenyl succinate–modified depolymerized waxy corn starch (DWxCn), waxy rice starch (DWxRc), phytoglycogen, whey protein concentrate (80%, WPC), whey protein isolate (WPI), and α‐lactalbumin (α‐L) to determine their potential as carriers of bioactive compounds under different environmental conditions. After enzyme modification and particle size characterization, glass transition temperature and moisture isotherms were used to characterize the systems. DWxCn and DWxRc had increased water sorption compared to native starch. The level of octenyl succinate anhydrate (OSA) modification (3% and 7%) did not reduce the water sorption of the DWxCn and phytoglycogen samples. The Guggenheim–Andersen–de Boer model indicated that native waxy corn had significantly (P < 0.05) higher water monolayer capacity followed by 3%‐OSA‐modified DWxCn, WPI, 3%‐OSA‐modified DWxRc, α‐L, and native phytoglycogen. WPC had significantly lower water monolayer capacity. All Tg values matched with the solid‐like appearance of the biopolymers. Native polysaccharides and whey proteins had higher glass transition temperature (Tg) values. On the other hand, depolymerized waxy starches at 7%‐OSA modification had a “melted” appearance when exposed to environments with high relative humidity (above 70%) after 10 days at 23 °C. The use of depolymerized and OSA‐modified polysaccharides blended with proteins created more stable blends of biopolymers. Hence, this biopolymer would be suitable for materials exposed to high humidity environments in food applications.     

非常规蛋白基木材胶黏剂研究现状及发展前景

介绍了动物和植物型非常规蛋白资源的种类及其制备蛋白基木材胶黏剂的研究现状和存在的问题,展望了非常规蛋白胶黏剂的发展前景。     

Soret and Dufour effects between two rectangular plane walls with heat source/sink

This study addresses the thermo‐diffusion and the diffusion‐thermo phenomena in a semi‐infinite absorbent channel whose walls are contracting/expanding, with heat source/sink effects. The governing partial differential equations with suitable boundary conditions are transformed to a system of dimensionless ordinary differential equations. An analytic solution of the problem has been found using a technique called homotopy analysis method (HAM). HAM gives consistently valid answers to the problem over an extensive variety of parameters and also provides better accuracy. To validate the analytical results, a comparison has been presented with a numerical solution calculated by using the parallel shooting method. The effects of dimensionless parameters, that is, deformation parameter, Reynolds number, Soret and Dufour numbers, and heat source/sink parameter on the expressions of velocity, temperature, and concentration profiles are analyzed graphically to understand the physics of the deformable channel. It has been noted that the velocity across the channel is higher for the expanding channel, as compared to that for the contracting channel. Also the Soret and Dufour number increases the temperature of the fluid, and decreases the concentration. The temperature profile has an increasing behavior in the case of heat source, and a decreasing behavior in the case of heat sink.