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Glenn McKinnon posted an update 7 months ago
In a previous work, we defined a novel HIV-1 fusion inhibitor peptide (E1P47) with a broad spectrum of activity against viruses from different clades, subtypes, and tropisms. With the aim to enhance its efficacy, in the present work we address the design and synthesis of several peptide amphiphiles (PAs) based on the E1P47 peptide sequence to target the lipid rafts of the cell membrane where the cell-cell fusion process takes place. We report the synthesis of novel PAs having a hydrophobic moiety covalently attached to the peptide sequence through a hydrophilic spacer of polyethylene glycol. Characterization of self-assembly in condensed phase and aqueous solution as well as their interaction with model membranes was analyzed by several biophysical methods. Our results demonstrated that the length of the spacer of polyethylene glycol, the position of the peptide conjugation as well as the type of the hydrophobic residue determine the antiviral activity of the construct. Peptide amphiphiles with one alkyl tail either in C-terminus (C-PAmonoalkyl) or in N-terminus (N-PAmonoalkyl) showed the highest anti-HIV-1 activities in the cellular model of TZM-bl cells or in a preclinical model of the human mucosal tissue explants.Nanoscale zero-valent iron (nZVI) has become one of the most used engineered nanoparticles for soil remediation. However, isolating nZVI particles from a complex soil matrix for their accurate particle characterizations and transport distance measurements is still challenging. Here, this study established a new analysis approach combining ultrasound-assisted solvent extraction, magnetic separation, and single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) analysis to isolate nZVI particles from soils and quantify their concentration and size. The interference from natural Fe-containing substances on nZVI analysis could be efficiently minimized by magnetic separation and dilution. After the optimization of extraction solvent type/concentration (i.e., 2.5 mM tetrasodium pyrophosphate) and ultrasonication time (i.e., 30 min), acceptable recoveries in both particle number (62.0 ± 10.8%-96.1 ± 4.8%) and Fe mass (70.6 ± 12.0%-119 ± 18%) could be achieved for different sizes (50 and 100 nm) and concentrations (50, 100, and 500 μg g-1) of spiked nZVI from six soils. The detection limits of particle size and concentration were approximately 43.1 nm and 50 μg nZVI per gram soil, respectively. These results provide a feasible approach to quantify the nZVI concentration and size in complex soil matrices, which will allow the improvements to characterize and track the nZVI particles in the field, promote the use of nZVI particles for soil remediation, and better assess their environmental implications.A new reductive strategy for the stereo- and regioselective synthesis of functionalized isoquinuclidines has been developed. Pivoting on the chemoselective iridium(I)-catalyzed reductive activation of β,γ-unsaturated δ-lactams, the efficiently produced reactive dienamine intermediates readily undergo cycloaddition reactions with a wide range of dienophiles, resulting in the formation of bridged bicyclic amine products. This new synthetic approach was extended to aliphatic starting materials, resulting in the efficient formation of cyclohexenamine products, and readily applied as the key step in the shortest (five-step) total synthesis of vinca alkaloid catharanthine to date, proceeding via its elusive biosynthetic precursor, dehydrosecodine.Skin tissue is regenerated by the combinational function of skin cells, extracellular matrix (ECM), and bioactive molecules. As an artificial ECM, supramolecular hydrogels exhibited outstanding capability to mimic the physical properties of ECM. However, the lack of biochemical function in supramolecular hydrogels has limited further tissue engineering applications. Here, we developed self-assembling supramolecular drug delivery hydrogels to mimic the skin tissue regeneration process. The supramolecular hydrogels were prepared to encapsulate fibroblasts by the host-guest interaction of cyclodextrin-modified gelatin (GE-CD) and adamantane-modified hyaluronate (Ad-HA) in conjugation with human growth hormone (hGH) for accelerated skin tissue regeneration. In vitro, GE-CD/Ad-HA-hGH hydrogels showed highly facilitated cell growth by the controlled hGH delivery. After a subcutaneous injection into the back of mice, IVIS imaging of bioengineered fibroblasts to express red fluorescence protein (RFP) revealed prolonged cell survival and proliferation in the supramolecular hydrogels for more than 21 days. We could also observe the improved skin tissue regeneration by the facilitated fibroblast proliferation with angiogenesis. Taken together, we could confirm the feasibility of biomimetic supramolecular drug delivery GE-CD/Ad-HA-hGH hydrogels for various tissue engineering applications.Room-temperature phosphorescence (RTP) with carbon dots (CDs) can be exploited further if the mechanism of trap-state-mediated triplet-state energy transfer is understood and controlled. Herein, we developed an in situ calcination method for the preparation of a CDs@ZnAl2O4 composite material that exhibits unique UV and visible light-excitable ultra-broad-band RTP. The ZnAl2O4 matrix can protect the triplet emissions of CDs by the confinement effect and spin-orbit coupling. JAK assay In addition, benefitting from the efficient energy transfer between the inorganic trap state and the triplet state of CDs, the special yellow to red RTP of CDs@ZnAl2O4 composites can be realized. A slow-decaying phosphorescence at 570 nm with a lifetime of 1.05 s and a fast-decaying phosphorescence at 400 nm with a lifetime of 0.41 s were observed with UV irradiation of 290 nm, which originated from the surface and core triplet states of CDs, respectively. Based on the unique RTP performance, anti-counterfeiting and information encryption were successfully realized using the CDs@ZnAl2O4 composites with LED light or UV light.The applications of bioconjugation chemistry are rapidly expanding, and the addition of new strategies to the bioconjugation and ligation toolbox will further advance progress in this field. Herein, we present a detailed study of the Diels-Alder cycloaddition (DAC) reaction between pentafulvenes and maleimides in aqueous solutions and investigate the reaction as an emerging bioconjugation strategy. The DAC reactions were found to proceed efficiently, quantitatively yielding cycloadducts with reaction rates ranging up to ∼0.7 M-1 s-1 for a series of maleimides, including maleimide-derivatized peptides and proteins. The absence of cross-reactivity of the pentafulvene with a large panel of functional (bio)molecules and biological media further demonstrated the bioorthogonality of this approach. The utility of the DAC reaction for bioorthogonal bioconjugation applications was further demonstrated in the presence of biological media and proteins, as well as through protein derivatization and labeling, which was comparable to the widely employed sulfhydryl-maleimide coupling chemistry.
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