5 research outputs found

    Specific Turn-On Fluorescent Probe with Aggregation-Induced Emission Characteristics for SIRT1 Modulator Screening and Living-Cell Imaging

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    SIRT1 is an important protein that catalyzes the nicotinamide adenine dinucleotide (NAD)<sup>+</sup>-dependent deacetylation reaction, which is regarded as a novel target to treat metabolic disorders and aging-related diseases. However, there is lack of appropriate approach for SIRT1 modulator screening and bioimaging of SIRT1 in living cells. We designed and synthesized a “turn-on” fluorescent probe by connecting a specifically recognized peptide to tetraphenylethene core. It exhibits excellent selectivity and sensitivity in homogeneous measurement of SIRT1 activity for screening both SIRT1 inhibitors and activators. 20­(S)-ginsenoside Rg<sub>3</sub> and ophiopogonin D′ were found to activate SIRT1. It was also successfully applied to monitor SIRT1 modulation in the cardiomyocytes as well as in the wild-type and SIRT1<sup>–/–</sup> mesenchymal stem cells

    Biscysteine-Bearing Peptide Probes To Reveal Extracellular Thiol–Disulfide Exchange Reactions Promoting Cellular Uptake

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    In recent years, delivery systems based on the incorporation of thiols/disulfides have been extensively explored to promote the intracellular delivery of biological cargoes. However, it remains unclear about the detailed processes of thiol–disulfide exchanges taking place on the cell surface and how the exchange reactions promote the cellular uptake of cargoes bearing thiols or disulfide bonds. In this work, we report the rational design of biscysteine motif-containing peptide probes with substantially different ring-closing property and how these peptide probes were employed to explore the thiol–disulfide exchanges on the cell surface. Our results show that extensive thiol–disulfide exchanges between peptides and exofacial protein thiols/disulfides are involved in the cellular uptake of these peptide probes, and importantly glutathione (GSH) exported from the cytosols participates extensively in the exchange reactions. Cysteine−glycine−cysteine (CGC)-containing peptide probes can be more efficiently taken up by cells compared to other probes, and we suggested that the driving force for the superior cellular uptake arises from very likely the unique propensity of the CGC motif in forming doubly bridged disulfide bonds with exofacial proteins. Our probe-based strategy provides firsthand information on the detailed processes of the exchange reactions, which would be of great benefit to the development of delivery systems based on the extracellular thiol–disulfide exchanges for intracellular delivery of biologics

    Controlling Electron/Hole Recombination in Near-Infrared Polymer Phototransistors through an Insulation Medium: A Pathway to Ultrahigh Photosensitivity

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    In near-infrared (NIR) polymer phototransistors, the photoresponse is proportional to the turn-on voltage shift (ΔVth). Due to the narrow band gap of NIR polymers, the ΔVth value is usually small. However, the use of a single bulk heterojunction (BHJ) layer has a minimal effect on increasing the value of ΔVth. This is because doping with high concentrations of acceptors results in strong current traps and accelerates electron/hole recombination. In this work, a new strategy is proposed to control the recombination of electrons/holes. By doping an insulating medium made of polystyrene (PS) into BHJs, PC61BM:PS:PDPP3T-based ternary NIR phototransistors with high acceptor concentrations were prepared by using a one-step film transfer method (FTM). Compared with a PC61BM:PDPP3T-based binary device (1:1), a ternary device (1:1:1) exhibited a significant performance improvement. The ΔVth value (∼29.5 ± 1.0 V) increased by approximately 4-fold, the Iph/Idark (∼4.4 × 106) increased by a factor of 3000 to 4000-fold, and the dark current decreased by 2–3 orders of magnitude (@ Vg = 0 V). Additionally, the ternary devices demonstrated excellent performance across a wide ternary ratio range (1:1:1 to 4:2:1)

    The Interplay of Disulfide Bonds, α‑Helicity, and Hydrophobic Interactions Leads to Ultrahigh Proteolytic Stability of Peptides

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    The contribution of noncovalent interactions to the stability of naturally occurring peptides and proteins has been generally acknowledged, though how these can be rationally manipulated to improve the proteolytic stability of synthetic peptides remains to be explored. In this study, a platform to enhance the proteolytic stability of peptides was developed by controllably dimerizing them into α-helical dimers, connected by two disulfide bonds. This platform not only directs peptides toward an α-helical conformation but permits control of the interfacial hydrophobic interactions between the peptides of the dimer. Using two model dimeric systems constructed from the N-terminal α-helix of RNase A and known inhibitors for the E3 ubiquitin ligase MDM2 (and its homologue MDMX), a deeper understanding into the interplay of disulfide bonds, α-helicity, and hydrophobic interactions on enhanced proteolytic stability was sought out. Results reveal that all three parameters play an important role on attaining ultrahigh proteolytic resistance, a concept that can be exploited for the development of future peptide therapeutics. The understanding gained through this study will enable this strategy to be tailored to new peptides because the proposed strategy displays substantial tolerance to sequence permutation. It thus appears promising for conveniently creating prodrugs composed entirely of the therapeutic peptide itself (i.e., in the form of a dimer)

    Insight into the Extreme Side Reaction between LiNi<sub>0.5</sub>Co<sub>0.2</sub>Mn<sub>0.3</sub>O<sub>2</sub> and Li<sub>1.3</sub>Al<sub>0.3</sub>Ti<sub>1.7</sub>(PO<sub>4</sub>)<sub>3</sub> during Cosintering for All-Solid-State Batteries

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    All-solid-sate batteries (ASSBs) with a NASICON-type solid-state electrolyte (SSE) of Li1.3Al0.3Ti1.7(PO4)3 (LATP) can be accepted as a promising candidate to significantly improve safety and energy density due to their high oxidation potential and high ionic conductivity. However, thermodynamic instability between the cathode and LATP is scarcely investigated during cosintering preparation for the integrated configuration of ASSBs. Herein, the structural compatibility between commercially layered LiNi0.5Co0.2Mn0.3O2 (NCM523) and LATP SSE was systematically investigated by cosintering at 600 °C. It is noticeable that an extreme side reaction between Li from NCM523 and phosphate from LATP happens during its cosintering process, leading to a severe phase transition from a layered to a spinel structure with high Li/Ni mixing. Consequently, the capacity of NCM523 is lost during the preparation of the NCM523–LATP composite cathode. Based on this, we suggested that the interface modification of the NCM523/LATP interface is valued significantly to inhibit this extreme side reaction, quickening the application of LATP-based ASSBs