Design,Synthesis, and Self-Assembly Studies of a Suite of Monodisperse,Facially Amphiphilic,Protein–Dendron Conjugates

The custom design of protein–dendron amphiphilic macromolecules is at the forefront of macromolecular engineering. Macromolecules with this architecture are very interesting because of their ability to self-assemble into various biomimetic nanoscopic structures. However, to date, there are no reports on this concept due to technical challenges associated with the chemical synthesis. Towards that end, herein, a new chemical methodology for the modular synthesis of a suite of monodisperse, facially amphiphilic, protein–dendron bioconjugates is reported. Benzyl ether dendrons of different generations (G1–G4) are coupled to monodisperse cetyl ethylene glycol to form macromolecular amphiphilic activity-based probes (AABPs) with a single protein reactive functionality. Micelle-assisted protein labeling technology is utilized for site-specific conjugation of macromolecular AABPs to globular proteins to make monodisperse, facially amphiphilic, protein–dendron bioconjugates. These biohybrid conjugates have the ability to self-assemble into supramolecular protein nanoassemblies. Self-assembly is primarily mediated by strong hydrophobic interactions of the benzyl ether dendron domain. The size, surface charge, and oligomeric state of protein nanoassemblies could be systematically tuned by choosing an appropriate dendron or protein of interest. This chemical method discloses a new way to custom-make monodisperse, facially amphiphilic, protein–dendron bioconjugates.     

Capsiate Intake with Exercise Training Additively Reduces Fat Deposition in Mice on a High-Fat Diet,but Not without Exercise Training

While exercise training (ET) is an efficient strategy to manage obesity, it is recommended with a dietary plan to maximize the antiobesity functions owing to a compensational increase in energy intake. Capsiate is a notable bioactive compound for managing obesity owing to its capacity to increase energy expenditure. We aimed to examine whether the antiobesity effects of ET can be further enhanced by capsiate intake (CI) and determine its effects on resting energy expenditure and metabolic molecules. Mice were randomly divided into four groups (n = 8 per group) and fed high-fat diet. Mild-intensity treadmill ET was conducted five times/week; capsiate (10 mg/kg) was orally administered daily. After 8 weeks, resting metabolic rate and metabolic molecules were analyzed. ET with CI additively reduced the abdominal fat rate by 18% and solely upregulated beta-3-adrenoceptors in adipose tissue (p = 0.013) but did not affect the metabolic molecules in skeletal muscles. Surprisingly, CI without ET significantly increased the abdominal fat rate (p = 0.001) and reduced energy expenditure by 9%. Therefore, capsiate could be a candidate compound for maximizing the antiobesity effects of ET by upregulating beta-3-adrenoceptors in adipose tissue, but CI without ET may not be beneficial in managing obesity.     

Synthesis of Long-Chain β-Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

In the quest for new antibacterial agents, a series of novel long- and medium-chain mono- and disubstituted β-lactones was developed. Their activity against three pathogenic mycobacteria—M. abscessus, M. marinum, and M. tuberculosis—was assessed by the resazurin microtiter assay (REMA). Among the 16 β-lactones synthesized, only 3-hexadecyloxetan-2-one (VM005) exhibited promising activity against M. abscessus, whereas most of the β-lactones showed interesting activities against M. marinum, similar to that of the classical antibiotic, isoniazid. Regarding M. tuberculosis, six compounds were found to be active against this mycobacterium, with β-lactone VM008 [trans-(Z)-3-(hexadec-7-en-1-yl)-4-propyloxetan-2-one] being the best growth inhibitor. The promising antibacterial activities of the best compounds in this series suggest that these molecules may serve as leads for the development of much more efficient antimycobacterial agents.     

The effect of Na addition on the first hydrogen absorption kinetics of cast hypoeutectic Mg–La alloys

With superior properties of Mg such as high hydrogen storage capacity (7.6 wt% H/MgH₂), low price, and low density, Mg has been widely studied as a promising candidate for solid-state hydrogen storage systems. However, a harsh activation procedure, slow hydrogenation/dehydrogenation process, and a high temperature for dehydrogenation prevent the use of Mg-based metal hydrides for practical applications. For these reasons, Mg-based alloys for hydrogen storage systems are generally alloyed with other elements to improve hydrogen sorption properties. In this article, we have added Na to cast Mg–La alloys and achieved a significant improvement in hydrogen absorption kinetics during the first activation cycle. The role of Na in Mg–La has been discussed based on the findings from microstructural observations, crystallography, and first principles calculations based on density functional theory. From our results in this study, we have found that the Na doped surface of Mg–La alloy systems have a lower adsorption energy for H₂ compared to Na-free surfaces which facilitates adsorption and dissociation of hydrogen molecules leading to improvement of absorption kinetic. The effect of Na on the microstructure of these alloys, such as eutectic refinement and a density of twins is not highly correlated with absorption kinetics.     

Pull-Down of Metalloproteins in Their Native States by Using Desthiobiotin-Based Probes

One-third of all proteins are estimated to require metals for structural stability and/or catalytic activity. Desthiobiotin probes containing metal binding groups can be used to capture metalloproteins with exposed active-site metals under mild conditions so as to prevent changes in metallation state. The proof-of-concept was demonstrated with carbonic anhydrase (CA), an open active site, Zn²⁺-containing protein. CA was targeted by using sulfonamide derivatives. Linkers of various lengths and structures were screened to determine the optimal structure for capture of the native protein. The optimized probes could selectively pull down CA from red blood cell lysate and other protein mixtures. Pull-down of differently metallated CAs was also investigated.