A new tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol ligand 3 has been prepared by a triple Cu(I)-catalyzed alkyne−azide 1,3-dipolar cycloaddition (CuAAC). Ligand 3 forms a stable complex with CuCl, ...which catalyzes the Huisgen 1,3-dipolar cycloaddition on water or under neat conditions. Low catalyst loadings, short reaction times at room temperature, and compatibility with free amino groups make 3·CuCl an outstanding catalyst for CuAAC.
The design of catalysts with greater control over catalytic activity and stability is a major challenge with substantial impact on fundamental chemistry and industrial applications. Due to their ...unparalleled diversity, selectivity, and efficiency, enzymes are promising models for next-generation catalysts, and considerable efforts have been devoted to incorporating the principles of their mechanisms of action into artificial systems. We report a heretofore undocumented catalyst design that introduces fullerenes to the field of biocatalysis, which we refer to as fullerene nanocatalysts, and that emulates enzymatic active sites through multifunctional self-assembled nanostructures. As a proof-of-concept, we mimicked the reactivity of hydrolases using fullerene nanocatalysts functionalized with the basic components of the parent enzyme with remarkable activity. Owing to the versatile amino acid-based functionalization repertoire of fullerene nanocatalysts, these next-generation carbon/biomolecule hybrids have potential to mimic the activity of other families of enzymes and, therefore, offer new perspectives for the design of biocompatible, high-efficiency artificial nanocatalysts.
The gelation of L-Tyr(tBu)-OH in tetrahydrofuran (THF) was discovered serendipitously. It was noted that this tremendously low molecular weight (LMW) compound has the ability to gel a wide variety of ...organic solvents (e.g., N,N-Dimetylformamide (DMF), THF, butanol, toluene), even in very low concentrations (i.e., 0.1 wt/v% in DMF). Addition of bases such as NaOH and piperidine enhanced the gel property. By changing the side-chain protecting group to tert-butyldimethylsilyl (TBDMS), a fluoride ion-responsive organogel was also acquired. This new organogelator responded fluoride ion concentration as low as 0.2 ppm. Characterization of microstructures and gel behaviours were studied by powder X-Ray diffraction spectroscopy (XRD), transmission electron microscopy (TEM), rheological measurements and molecular dynamics (MD) simulations. Experimental observations and theoretical simulations consistently show a fibre-like structure of the gel, in which the organogelator molecules are held together via a dense network of hydrogen bonds, and via van der Waals interactions between hydrophobic groups.
Enzyme mimicry is a topic of considerable interest in the development of multifunctional biomimetic materials. Mimicking enzyme activity is a major challenge in biomaterials research, and artificial ...analogs that simultaneously recapitulate the catalytic and metabolic activity of native enzymes are considered to be the ultimate goal of this field. This consensus may be challenged by self‐assembling multifunctional nanostructures to develop close‐to‐fidelity enzyme mimics. Here, the ability of fullerene nanostructures decorated with active units to form enzyme‐like materials that can mimic phosphatases in a metal‐free manner is presented. These nanostructures self‐assemble into nanoclusters forming multiple random active sites that can cleave both phosphomonoesters and phosphodiesters while being more specific for the phosphomonoesters. Moreover, they are reusable and show an increase in catalytic activity over multiple cycles similar to their natural counterparts. In addition to having enzyme‐like catalytic properties, these nanocatalysts imitate the biological functions of their natural analogs by inducing biomineralization and osteoinduction in preosteoblast and mesenchymal stem cells in vitro studies.
In this study, a simple module for mimicking various functions and features of phosphatase enzyme is developed. The approach uses fullerenol nanocages, as a scaffold that is functionalized to perform rapid catalysis, biomineralization, and stem cell differentiation at the same time.
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•A sensitive and cost-effective enzyme-free sensor system for the effective electrooxidation of acetylcholine (ACh)•A novel fullerenzyme-based catalyst (F-HS) for the quick detection ...and diagnosis of Alzheimer's.•A sensitive and selective fullerenzymes based electrochemical sensor for quantitative ACh detection in human serum samples with high accuracy.•High repeatable, reproducible, and sensitive ACh sensor.
The design of sensitive and cost-effective enzyme-free sensor systems for the effective electrooxidation of acetylcholine (ACh) plays a key role in following up on Alzheimer’s disease. We report a fullerenzyme-based catalyst (F-HS) for the electrochemical detection of ACh that mimics enzymatic active sites using multifunctional self-assembled nanostructures. As a proof-of-concept, histidine and serine amino acid-based functionalization of fullerenzymes was used, along with embedded nickel ions (F-HS-Ni), which tend to coordinate with the nitrogen of the imidazole ring of the histidine moiety. Further, the electrode modifier properties of the resulting material were examined for sensor applications. Enhanced cyclic voltammetry and chronoamperometric measurements affirmed that the F-HS-Ni material displayed the most prominent activity for the electrocatalytic oxidation of ACh, allowing an amperometric response in a linear range of ACh concentrations of 20–6000 μM with a low detection limit of 8.01 μM. Furthermore, the platform allows for the detection of ACh with a good rate of recovery in human serum samples, offering a good potential method for the quick detection and diagnosis of Alzheimer’s.
Uranyl (UO2(2+)), the predominant aerobic form of uranium, is present in the ocean at a concentration of ~3.2 parts per 10(9) (13.7 nM); however, the successful enrichment of uranyl from this vast ...resource has been limited by the high concentrations of metal ions of similar size and charge, which makes it difficult to design a binding motif that is selective for uranyl. Here we report the design and rational development of a uranyl-binding protein using a computational screening process in the initial search for potential uranyl-binding sites. The engineered protein is thermally stable and offers very high affinity and selectivity for uranyl with a Kd of 7.4 femtomolar (fM) and >10,000-fold selectivity over other metal ions. We also demonstrated that the uranyl-binding protein can repeatedly sequester 30-60% of the uranyl in synthetic sea water. The chemical strategy employed here may be applied to engineer other selective metal-binding proteins for biotechnology and remediation applications.
GPR56/ADGRG1 is an adhesion G protein-coupled receptor (GPCR) and mutations on this receptor cause cortical malformation due to the over-migration of neural progenitor cells on brain surface. At pial ...surface, GPR56 interacts with collagen III, induces Rho-dependent activation through Gα
and inhibits the neuronal migration. In human glioma cells, GPR56 inhibits cell migration through Gα
-dependent Rho pathway. GPR56-tetraspanin complex is known to couple Gα
. GPR56 is an aGPCR that couples with various G proteins and signals through different downstream pathways. In this study, bilateral frontoparietal polymicrogyria (BFPP) mutants disrupting GPR56 function but remaining to be expressed on plasma membrane were used to study receptor signalling through Gα
, Gα
and Gα
with BRET biosensors. GPR56 showed coupling with all three G proteins and activated heterotrimeric G protein signalling upon stimulation with Stachel peptide. However, BFPP mutants showed different signalling defects for each G protein indicative of distinct activation and signalling properties of GPR56 for Gα
, Gα
or Gα
. β-arrestin recruitment was also investigated following the activation of GPR56 with Stachel peptide using BRET biosensors. N-terminally truncated GPR56 showed enhanced β-arrestin recruitment; however, neither wild-type receptor nor BFPP mutants gave any measurable recruitment upon Stachel stimulation, pointing different activation mechanisms for β-arrestin involvement.
Aggregation-induced emission (AIE) is a phenomenon where certain molecules or materials become highly luminescent when they aggregate or come together in a condensed state, such as a solid or a ...solution. Moreover, new molecules which show AIE properties are designed and synthesized for various applications like imaging, sensing, and optoelectronics. 2,3,5,6-Tetraphenylpyrazine (TPP) is one of the well-established examples of AIE. Herein, 2,3,5,6-tetraphenyl-1,4-dioxin (TPD) and 2,3,4,5-tetraphenyl-4H-pyran-4-one (TPPO), which are old molecules with TPP similarity, were studied, and new insights in terms of structure and aggregation-caused quenching (ACQ)/AIE properties were gained by means of theoretical calculations. Those calculations performed on TPD and TPPO aimed to provide a better understanding of their molecular structures and how they affect their luminescence properties. This information could be used to design new materials with improved AIE properties or to modify existing materials to overcome ACQ.
This study focuses on creating a specialized nanogel for targeted drug delivery in cancer treatment, specifically targeting prostate cancer. This nanogel (referred to as SGK 636/Peptide 563/PEtOx ...nanogel) is created using hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEtOx) through a combination of living/cationic ring‐opening polymerization (CROP) and alkyne‐azide cycloaddition (CuAAC) “click” chemical reactions. A fluorescent probe (BODIPY) is also conjugated with the nanogel to monitor drug delivery. The characterizations through 1H‐NMR, and FT‐IR, SEM, TEM, and DLS confirm the successful production of uniform, and spherical nanogels with controllable sizes (100 to 296 nm) and stability in physiological conditions. The biocompatibility of nanogels is evaluated using MTT cytotoxicity assays, revealing dose‐dependent cytotoxicity. Drug‐loaded nanogels exhibited significantly higher cytotoxicity against cancer cells in vitro compared to drug‐free nanogels. Targeting efficiency is examined using both peptide‐conjugated and peptide‐free nanogels, with the intracellular uptake of peptide 563‐conjugated nanogels by tumor cells being 60‐fold higher than that of nanogels without the peptide. The findings suggest that the prepared nanogel holds great potential for various drug delivery applications due to its ease of synthesis, tunable functionality, non‐toxicity, and enhanced intracellular uptake in the tumor region.
This study emphisizes an innovative PEtOx‐based nanogel tailored for targeted drug delivery in prostate cancer. Developed using click chemistry, a valuable technique for chemical synthesis, it exhibits consistent nanogel formation with customizable sizes. In vitro, drug‐loaded nanogel exhibits potent cytotoxicity against cancer cells. Notably, peptide‐conjugated nanogels significantly boost tumor cell uptake, showcasing promising promising potential for effective cancer drug delivey.
Here we present self-assembled polymeric micelles as potential delivery systems for therapeutic agents with highly tunable properties. The major goal of this study is to design breast and prostate ...cancer specific targeting peptide modified PEtOx- co -PEI- b -PCL block copolymer based micelles as a targetable carrier system in cancer treatment. For this, a series of micelles based on poly(2-ethyl-2-oxazoline)- co -polyethyleneimine- block -poly(ε-caprolactone) P(EtOx- co -EI)- b -PCL copolymers with two different proportions of PEI (30% and 60% hydrolysis degrees of PEtOx) were successfully prepared. The block copolymers were synthesized using a combination of living cationic ring-opening polymerization and a copper( i )-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction. Then, peptide 18 and peptide 563 were conjugated to P(EtOx- co -EI)- b -PCL through a thiol–ene click-type reaction to obtain the desired tumor-targeting. The structural properties of the copolymers were confirmed by 1 H NMR, FT-IR, UV-Vis spectrometry and GPC. Peptide and non-peptide-conjugated micelles with particle sizes between 82 ± 0.6 and 170 ± 10.7 nm were obtained by self-assembly with two different chain lengths of PEI blocks. The micelles containing the 60% PEI block showed increased zeta potential values. The cytotoxicity of the copolymers was evaluated under in vitro conditions. Overall, our results indicate that the micelles prepared with peptide-conjugated block copolymers can be used as potential nanocarriers for targeted therapeutic delivery systems.