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Despite their high potency, the widespread implementation of natural antimicrobial peptides is still challenging due to their low scalability and high hemolytic activities. Herein, we address these issues by employing a modular approach to mimic the key amino acid residues present in antimicrobial peptides, such as lysine, leucine, and serine, but on the highly biocompatible poly(ethylene glycol) (PEG) backbone. Ginkgolic A series of these PEG-based peptides (PEGtides) were developed using functional epoxide monomers, corresponding to each key amino acid, with several possessing highly potent bactericidal activities and controlled selectivities, with respect to their hemolytic behavior. The critical role of the composition and the structure of the PEGtides in their selectivities was further supported by coarse-grained molecular dynamic simulations. This modular approach is anticipated to provide the design principles necessary for the future development of antimicrobial polymers.Chemokines are secreted proteins that regulate leukocyte migration during inflammatory responses by signaling through chemokine receptors. Full length CC chemokine ligand 14, CCL14(1-74), is a weak agonist for the chemokine receptor CCR1, but its activity is substantially enhanced upon proteolytic cleavage to CCL14(9-74). CCL14 is O-glycosylated at Ser7, adjacent to the site of proteolytic activation. To determine whether glycosylation regulates the activity of CCL14, we used native chemical ligation to prepare four homogeneously glycosylated variants of CCL14(1-74). Each protein was assembled from three synthetic peptide fragments in "one-pot" using two sequential ligation reactions. We show that while glycosylation of CCL14(1-74) did not affect CCR1 binding affinity or potency of activation, sialylated variants of CCL14(1-74) exhibited reduced activity after treatment with plasmin compared to nonsialylated forms. These data indicate that glycosylation may influence the biological activity of CCL14 by regulating its conversion from the full-length to the truncated, activated form.Soft printed electronics exhibit unique structures and flexibilities suited for a plethora of wearable applications. However, forming scalable, reliable multilayered electronic devices with heterogeneous material interfaces on soft substrates, especially on porous and anisotropic structures, is highly challenging. In this study, we demonstrate an all-inkjet-printed textile capacitor using a multilayered structure of bilayer polymer dielectrics and particle-free metal-organic decomposition (MOD) silver electrodes. Understanding the inherent porous/anisotropic microstructure of textiles and their surface energy relationship was an important process step for successful planarization. The MOD silver ink formed a foundational conductive layer through the uniform encapsulation of individual fibers without blocking fiber interstices. Urethane-acrylate and poly(4-vinylphenol)-based bilayers were able to form a planarized dielectric layer on polyethylene terephthalate textiles. A unique chemical interaction at the interfaces of bilayer dielectrics performed a significant role in insulating porous textile substrates resulting in high chemical and mechanical durability. In this work, we demonstrate how textiles' unique microstructures and bilayer dielectric layer designs benefit reliability and scalability in the inkjet process as well as the use in wearable electronics with electromechanical performance.The hydrogen storage capacity of Pd nanoparticles (NPs) decreases as the particles become smaller; however, this reduced capacity is ameliorated by addition of Pt. In the present work, the hydrogen storage mechanism and structural transformations of core (Pd)-shell (Pt) (CS) and solid-solution (SS) NPs during hydrogen absorption and desorption (PHAD) processes are investigated. In situ X-ray absorption spectroscopy measurements were performed to study the evolution of electronic and local structures around Pd and Pt during PHAD. Under ambient conditions, Pd and Pt have distinct local structures. The Pd atomic pairs are more strained in CS NPs than in SS NPs. A similar behavior has been seen in CS NPs after PHAD. The Pd K-edge extended X-ray absorption fine structure data indicate that in CS and SS NPs a substantial fraction of the signal derives from Pd-Pd atomic pairs, indicating that Pd clusters remain present even after PHAD. PHAD causes a rearrangement of the interfacial structure, which becomes homogeneously distributed. The higher coverage of active bimetallic sites results in a higher observed hydrogen storage capacity in the SS phase.Exosomes are cell-derived vesicles containing heterogeneous active biomolecules such as proteins, lipids, mRNAs, receptors, immune regulatory molecules, and nucleic acids. They typically range in size from 30 to 150 nm in diameter. An exosome's surfaces can be bioengineered with antibodies, fluorescent dye, peptides, and tailored for small molecule and large active biologics. Exosomes have enormous potential as a drug delivery vehicle due to enhanced biocompatibility, excellent payload capability, and reduced immunogenicity compared to alternative polymeric-based carriers. Because of active targeting and specificity, exosomes are capable of delivering their cargo to exosome-recipient cells. Additionally, exosomes can potentially act as early stage disease diagnostic tools as the exosome carries various protein biomarkers associated with a specific disease. In this review, we summarize recent progress on exosome composition, biological characterization, and isolation techniques. Finally, we outline the exosome's clinical applications and preclinical advancement to provide an outlook on the importance of exosomes for use in targeted drug delivery, biomarker study, and vaccine development.Small molecule irreversible inhibitors are valuable tools for determining catalytically important active-site residues and revealing key details of the specificity, structure, and function of glycoside hydrolases (GHs). β-glucans that contain backbone β(1,3) linkages are widespread in nature, e.g., mixed-linkage β(1,3)/β(1,4)-glucans in the cell walls of higher plants and β(1,3)glucans in yeasts and algae. Commensurate with this ubiquity, a large diversity of mixed-linkage endoglucanases (MLGases, EC 3.2.1.73) and endo-β(1,3)-glucanases (laminarinases, EC 3.2.1.39 and EC 3.2.1.6) have evolved to specifically hydrolyze these polysaccharides, respectively, in environmental niches including the human gut. To facilitate biochemical and structural analysis of these GHs, with a focus on MLGases, we present here the facile chemo-enzymatic synthesis of a library of active-site-directed enzyme inhibitors based on mixed-linkage oligosaccharide scaffolds and N-bromoacetylglycosylamine or 2-fluoro-2-deoxyglycoside warheads.
My Website: https://www.selleckchem.com/products/ginkgolic-acid-s9432.html
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