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Exploring vinylene-linked nanoporous covalent organic framework (COF) materials has become a valuable research focus due to their various outstanding properties. However, only a few examples have been reported to construct vinylene-linked COFs, which seriously restricted their applications. Herein, two COFs linked by olefins TC-PT and TC-PB via the Knoevenagel condensation of 1,3,5-tris-(4-cyanomethylphenyl) benzene and 2,4,6-tris (4-formylphenyl)-1,3,5-triazine or 1,3,5-tris (4-formylphenyl) benzene were designed and constructed, which possessed high crystallinity, remarkable porosity, and high structural, chemical, and thermal stability. The two nanoporous organic framework materials prepared can be used for catalytic organic reaction of phenylboric acid and its derivatives driven efficiently by visible light. It is noted that TC-PT with a donor–acceptor structure presented excellent activity, yield, and recyclability. We believed that this work would provide some precious insights for developing functional vinylene-linked COFs. [ABSTRACT FROM AUTHOR]

The design and synthesis of a new class of laser light activatable tetrazoles with extended π-systems is reported. Upon 405 nm laser light irradiation, these bithiophene-substituted tetrazoles underwent extremely fast 1,3-dipolar cycloaddition reactions with dimethyl fumarate with second-order rate constants approaching 4000 M–1s–1. The resulting pyrazoline cycloadducts exhibited solvent-dependent red fluorescence, making these tetrazoles potentially useful as fluorogenic probes for detecting alkenes in vivo. [ABSTRACT FROM AUTHOR]

Impaired intestinal barrier function can impede the digestion and absorption of nutrients and cause a range of metabolic disorders, which are the main causes of intestinal disease. Evidence suggests that proper dietary protein intake can prevent and alleviate intestinal diseases. Egg white protein (EWP) has received considerable attention, because of its high protein digestibility and rich amino acid composition. Furthermore, bioactive peptides may have an increased repair effect due to their high degradation efficiency in the gut. In this study, we aimed to review the effects of EWP and its bioactive peptides on intestinal structural repair. The potential modulation mechanisms by which EWP and their peptides regulate the gut microbiota and intestinal barrier can be summarized as follows: (1) restoring the structure of the intestinal barrier to its intact form, (2) enhancing the intestinal immune system and alleviating the inflammatory response and oxidative damage, and (3) increasing the relative abundance of beneficial bacteria and metabolites. Further in-depth analysis of the coregulation of multiple signaling pathways by EWP is required, and the combined effects of these multiple mechanisms requires further evaluation in experimental models. Human trials can be considered to understand new directions for development.

Crude oil adhesion issues are widespread in the petroleum industry, leading to inefficient production and high maintenance costs. Developing efficient antifouling materials and investigating the microscopic adhesion mechanism are of substantial significance. In the present work, a superhydrophilic/underwater superoleophobic PAFC coating with excellent antifouling properties was constructed by the coordination-driven self-assembly of phytic acid (PA) and FeCl 3 (FC). The atomic force microscope (AFM) droplet probe technique was employed to elucidate the underlying mechanism of the anti-oil-adhesion property of the PAFC coating. Results showed that the PAFC modification achieved the optimum effect at a molar ratio of 1:3 between PA and Fe III . Applying a (3-aminopropyl)triethoxysilane (APTES) interlayer can effectively improve the performance of the PAFC coating on silica substrates. AFM droplet probe experiments indicated that the adhesion force between submerged micrometer-sized oil droplets and PAFC-modified substrates was significantly weaker than that with the untreated substrate. Meanwhile, the adhesion forces between oil droplets and surfaces were inversely proportional to the contact angle of the oil in water and were enhanced by higher salinity, lower collision velocity, and stronger loading force. The oil injection and wall sticking tests also confirmed the effectiveness of the PAFC modification in resisting the adhesion of crude oil.

The angiotensin-converting enzyme (ACE) inhibitory peptide QIGLF derived from egg white was shown to have significant in vivo antihypertensive effects in our previous study, but the intervention mechanisms at the metabolic level are still unclear. The UPLC-QTOF/MS-based untargeted metabolomics approach was used to clarify the potential antihypertensive mechanisms of QIGLF in the serum of spontaneously hypertensive rats (SHRs). Multivariate statistical analysis showed a clear difference in the metabolite profiles between the QIGLF and model groups. The results suggested that eight potential biomarkers were identified, that is, adrenic acid, ursodeoxycholic acid, glycocholic acid, taurocholic acid, tryptophan, acetylindoxyl, tyrosine, and 2-phenylethanol, which were mainly involved in aromatic amino acid biosynthesis and metabolism, biosynthesis of bile acid, and biosynthesis of unsaturated fatty acids. QIGLF might exert antihypertensive effects by improving endothelial dysfunction. This study provides a theoretical basis for future research and application of ACE inhibitory peptides in the prevention and improvement of hypertension.

Considering the multiple biological barriers before the entry of photosensitizers (PSs) into cytoplasm, it is of paramount importance to track PSs to elucidate their behaviors and distributions to guide the photodynamic therapy (PDT). Also, the developed PSs suffer from strong oxygen dependency. However, reports on such ideal theranostic platforms are rare. Herein, we developed a theranostic platform ( CMTP-2 ) based on the coumarin-based D-π-A system, which, for the first time, can reveal the holistic intracellular delivery pathway and near-infrared (NIR)-activated mitophagy to guide synergistic type-I PDT and photothermal therapy. The dynamic endo-lysosomal escape of CMTP-2 was monitored, as well as its changeable distributions in endosomes, lysosomes, and mitochondria, demonstrating the preferential accumulation in mitochondria at the end. Upon NIR-I irradiation, CMTP-2 generated toxic radicals and heat, triggering the execution of mitophagy and apoptosis. In vivo experiments on mice indicated that CMTP-2 under 808 nm irradiation realized complete cancer ablation, showing great potential for advancements in synergistic phototherapy.

The objective of this paper was to investigate the hydrolysis and transepithelial transport of egg white peptides in Caco-2 cell monolayers and everted rat sacs. Results showed that egg white peptides had higher permeability but lower degradation in Caco-2 cell monolayers than found for everted rat sacs. Peptides LGAKDSTRT, DGSRQPVDN, VNDLQGKTS, and GKKDPVLKD were identified from not only the basolateral (BL) side of Caco-2 cell monolayers but also the serous side of everted rat sacs, suggesting that these four peptides could be transported intact in both model systems. In addition, there were 24 peptides identified from the apical (AP) side of Caco-2 cell monolayers and the mucosal side of everted rat sacs, indicating potential resistance to hydrolysis by brush border membrane peptidases. Among these, peptides IRDLLER, YAEERYP, and IRNVLQPS were demonstrated as having dipeptidyl peptidase IV (DPP-IV) inhibitory activities with IC 50 values of 186.23 ± 15.25, 340.62 ± 4.73, and 598.28 ± 15.12 μM ( P < 0.05), respectively. Furthermore, molecular docking revealed that the DPP-IV inhibitory peptides were predicted to form hydrogen-bonds, π-π bonds, and charge interactions with the activity sites, especially the amino acid residues located in the S2 pocket of DPP-IV, potentially contributing to their DPP-IV inhibitory activities.

A small library of diarylsydnones (DASyds) was constructed based on aryl-pairing combinations and subjected to click reaction toward alkenes under photoirradiation with high efficiency. We were able to demonstrate the utility of DASyds for highly fluorescent turn-on ligation targeting the trans-cyclooct-4-en-1-ol moieties on protein.

Nonionic triblock copolymers, surfactant Pluronic F68 (PEO76-PPO29-PEO76), are widely used in industrial processes, such as foaming, emulsification, and stabilization. The behaviors of triblock copolymers such as the salt-dependent self-assembly in bulk solution and the irreversible adsorption at the oil/water interface are mainly focused to explore their effects on the interaction forces between nano-spacing interfaces of oil droplets. In this study, the atomic force microscopy (AFM) technique was employed to measure the drop interaction forces with different F68 bulk concentrations. All selected bulk concentrations (≥100 μM) of copolymers can ensure the formation of a stable layer structure of stretched polymer chains ("brush") at the oil/water interface, which behaved as a mechanical barrier at the interface. This study quantified the forces caused by the space hindrance of F68 copolymers both in the bulk phase and at the interface of oil/F68 aqueous solution during drop interaction. The effects of monovalent electrolyte (NaCl)-induced self-assembly behavior of triblock copolymers F68 in bulk solution on drop interaction forces were measured through the AFM technique.

A new bioorthogonal reactant pair, spiro[2.3]hex-1-ene (Sph) and 3,6-di(2-pyridyl)-s-tetrazine (DpTz), for the strain-promoted inverse electron-demand Diels-Alder cycloaddition, that is, tetrazine ligation, is reported. As compared to the previously reported strained alkenes such as trans-cyclooctene (TCO) and 1,3-disubstituted cyclopropene, Sph exhibits balanced reactivity and stability in tetrazine ligation with the protein substrates. A lysine derivative of Sph, SphK, was site-selectively incorporated into the extracellular loop regions (ECLs) of GCGR and GLP-1R, two members of class B G protein-coupled receptors (GPCRs) in mammalian cells with the incorporation efficiency dependent on the location. Subsequent bioorthogonal reactions with the fluorophore-conjugated DpTz reagents afforded the fluorescently labeled GCGR and GLP-1R ECL mutants with labeling yield as high as 68%. A multitude of functional assays were performed with these GPCR mutants, including ligand binding, ligand-induced receptor internalization, and ligand-stimulated intracellular cAMP accumulation. Several positions in the ECL3s of GCGR and GLP-1R were identified that tolerate SphK mutagenesis and subsequent bioorthogonal labeling. The generation of functional, fluorescently labeled ECL3 mutants of GCGR and GLP-1R should allow biophysical studies of conformation dynamics of this important class of GPCRs in their native environment in live cells.

The objective of this paper was to investigate the effects of terminal amino acids on the transport of oligopeptides across the Caco-2 cell monolayer. Ala-based tetra- and pentapeptides were designed, and the N- or C-terminal amino acid residues were replaced by different amino acids. The results showed that the oligopeptides had a wide range of transport permeability across the Caco-2 cell monolayer and could be divided into four categories: non-/poor permeability, low permeability, intermediate permeability, and good permeability. Tetrapeptides with N-terminal Leu, Pro, Ile, Cys, Met, and Val or C-terminal Val showed the highest permeability, with apparent permeability coefficient (P app ) values over 10 × 10 -6 cm/s (p < 0.05), suggesting that nonpolar hydrophobic aliphatic amino acids or polar sulfur-containing amino acids were the best for the transport of tetrapeptides. Pentapeptides with N- or C-terminal Tyr also showed high permeability levels, with P app values of about 10 × 10 -6 cm/s. The amino acids Glu, Asn, and Thr at the N terminus or Lys, Asp, and Arg at the C terminus were also beneficial for the transport of tetra- and pentapeptides, with P app values ranging from 1 × 10 -6 to 10 × 10 -6 cm/s. In addition, peptides with amino acids replaced at the N terminus generally showed higher permeability than those with amino acids replaced at the C terminus (p < 0.05), suggesting that N-terminal amino acids were more important for the transport of oligopeptides across the Caco-2 cell monolayer.

The genetically encoded photo-cross-linkers promise to offer a temporally controlled tool to map transient and dynamic protein-protein interaction complexes in living cells. Here we report the synthesis of a panel of 2-aryl-5-carboxytetrazole-lysine analogs (ACTKs) and their site-specific incorporation into proteins via amber codon suppression in Escherichia coli and mammalian cells. Among five ACTKs investigated, N-methylpyrroletetrazole-lysine (mPyTK) was found to give robust and site-selective photo-cross-linking reactivity in E. coli when placed at an appropriate site at the protein interaction interface. A comparison study indicated that mPyTK exhibits higher photo-cross-linking efficiency than a diazirine-based photo-cross-linker, AbK, when placed at the same location of the interaction interface in vitro. When mPyTK was introduced into the adapter protein Grb2, it enabled the photocapture of EGFR in a stimulus-dependent manner. The design of mPyTK along with the identification of its cognate aminoacyl-tRNA synthetase makes it possible to map transient protein-protein interactions and their interfaces in living cells.

The use of small, natural chemical reporters in conjunction with catalyst-free bioorthogonal reactions will greatly streamline protein labeling in a cellular environment with minimum perturbation to their function. Here we report the discovery of a 2-cyanobenzothiazole (CBT)-reactive peptide tag, CX10R7, from a cysteine-encoded peptide phage library using the phage-assisted interrogation of reactivity method. Fusion of CX10R7 with a protein of interest allows site-specific labeling of the protein with CBT both in vitro and on the surface of E. coli cells. Mutagenesis studies indicated that the reactivity and specificity of CX10R7 are attributed to the sequence environment, in which the residues surrounding cysteine help to stabilize the ligation product.

Reactive yet stable alkene reporters offer a facile route to studying fast biological processes via the cycloaddition-based bioorthogonal reactions. Here, we report the design and synthesis of a strained spirocyclic alkene, spiro[2.3]hex-1-ene (Sph), for an accelerated photoclick chemistry, and its site-specific introduction into proteins via amber codon suppression using the wild-type pyrrolysyl-tRNA synthetase/tRNA(CUA) pair. Because of its high ring strain and reduced steric hindrance, Sph exhibited fast reaction kinetics (k2 up to 34,000 M(-1) s(-1)) in the photoclick chemistry and afforded rapid (<10 s) bioorthogonal protein labeling.

Hen eggs are well-known for their biological functions beyond basic nutrition. In this study, the antihypertensive effect of peptide RVPSL from egg protein has been evaluated by an in vivo model. In addition, the mRNA levels of renin, AT1 receptor, angiotensin-converting enzyme (ACE), and AT2 receptor in the rat kidney were investigated through real-time polymerase chain reaction. The Ang I, Ang II, renin, and aldosterone concentrations of serum were also measured. Our results indicated that the blood pressure of the spontaneously hypertensive rats administered RVPSL for 4 weeks decreased significantly compared to that of the negative group. The mRNA levels of renin, ACE, and AT1 receptor in kidney also decreased significantly. The serum Ang II, renin, and aldosterone concentrations of the treatment group were reduced in comparison to those of the negative group. It is hoped this study will help our understanding and potential use of RVPSL in the treatment or prevention of hypertension.

The tetrazole-based photoclick chemistry has provided a powerful tool to image proteins in live cells. To extend photoclick chemistry to living organisms with improved spatiotemporal control, here we report the design of naphthalene-based tetrazoles that can be efficiently activated by two-photon excitation with a 700 nm femtosecond pulsed laser. A water-soluble, cell-permeable naphthalene-based tetrazole was identified that reacts with acrylamide with the effective two-photon cross-section for the cycloaddition reaction determined to be 3.8 GM. Furthermore, the use of this naphthalene-tetrazole for real-time, spatially controlled imaging of microtubules in live mammalian cells via the fluorogenic, two-photon-triggered photoclick chemistry was demonstrated.

A series of new isophorone derivatives (1-5), incorporating the heterocyclic ring or aza-crown-ether group, with large Stokes shifts (>140 nm), have been synthesized and characterized. 1-4 display aggregation-induced emission behaviors, while dye 5 is highly emissive in solution but quenched in the solid state. It was found that the tuning of emission color of the isophorone-based compounds in the solid state could be conveniently accomplished by changing the terminal substituent group. The photophysical properties in solution, aqueous suspension, and crystalline state, along with their relationships, are comparatively investigated. Crystallographic data of 1-4 indicate that the existence of multiple intermolecular hydrogen bonding interactions between the adjacent molecules restricts the intramolecular vibration and rotation and enables compounds 1-4 to emit intensely in the solid state. The size and growth processes of particles with different water fractions were studied using a scanning electron microscope, indicating that smaller globular nanoparticles in aqueous suspension are in favor of fluorescence emissions. The above results suggest that substituent groups have a great influence on their molecular packing, electronic structure, and aggregation-induced emission properties. In addition, fluorescence cell imaging experiment proved the potential application of 5.

Photoactivatable fluorescent probes are invaluable tools for the study of biological processes with high resolution in space and time. Numerous strategies have been developed in generating photoactivatable fluorescent probes, most of which rely on the photo-"uncaging" and photoisomerization reactions. To broaden photoactivation modalities, here we report a new strategy in which the fluorophore is generated in situ through an intramolecular tetrazole-alkene cycloaddition reaction ("photoclick chemistry"). By conjugating a specific microtubule-binding taxoid core to the tetrazole/alkene prefluorophores, robust photoactivatable fluorescent probes were obtained with fast photoactivation (∼1 min) and high fluorescence turn-on ratio (up to 112-fold) in acetonitrile/PBS (1:1). Highly efficient photoactivation of the taxoid-tetrazoles inside the mammalian cells was also observed under a confocal fluorescence microscope when the treated cells were exposed to either a metal halide lamp light passing through a 300/395 filter or a 405 nm laser beam. Furthermore, a spatially controlled fluorescent labeling of microtubules in live CHO cells was demonstrated with a long-wavelength photoactivatable taxoid-tetrazole probe. Because of its modular design and tunability of the photoactivation efficiency and photophysical properties, this intramolecular photoclick reaction based approach should provide a versatile platform for designing photoactivatable fluorescent probes for various biological processes., (© 2011 American Chemical Society)

Light-induced chemical reactions exist in nature, regulating many important cellular and organismal functions, e.g., photosensing in prokaryotes and vision formation in mammals. Here, we report the genetic incorporation of a photoreactive unnatural amino acid, p-(2-tetrazole)phenylalanine (p-Tpa), into myoglobin site-specifically in E. coli by evolving an orthogonal tRNA/aminoacyl-tRNA synthetase pair and the use of p-Tpa as a bioorthogonal chemical "handle" for fluorescent labeling of p-Tpa-encoded myoglobin via the photoclick reaction. Moreover, we elucidated the structural basis for the biosynthetic incorporation of p-Tpa into proteins by solving the X-ray structure of p-Tpa-specific aminoacyl-tRNA synthetase in complex with p-Tpa. The genetic encoding of this photoreactive amino acid should make it possible in the future to photoregulate protein function in living systems.

The nonsymmetrical spatial distribution of newly synthesized proteins in animal cells plays a central role in many cellular processes. Here, we report that a simple alkene tag, homoallylglycine (HAG), was co-translationally incorporated into a recombinant protein as well as endogenous, newly synthesized proteins in mammalian cells with high efficiency. In conjunction with a photoinduced tetrazole-alkene cycloaddition reaction ("photoclick chemistry"), this alkene tag further served as a bioorthogonal chemical reporter both for the selective protein functionalization in vitro and for a spatiotemporally controlled imaging of the newly synthesized proteins in live mammalian cells. This two-step metabolic alkene tagging-photocontrolled chemical functionalization approach may offer a potentially useful tool to study the role of spatiotemporally regulated protein synthesis in mammalian cells.

We report the direct observation of a bent geometry for a nonstabilized nitrile imine in a metal-coordination crystal. The photoinduced tetrazole ring rupture to release N(2) appears to depend on the size of voids around the N(3)-N(4) bond in the crystal lattice. We further observed the selective formation of the 1,3-addition product when a reactive nitrile imine was photogenerated in water. Overall, the bent nitrile imine geometry agrees with the 1,3-dipolar structure, a transient reactive species that mediates the photoinduced 1,3-dipolar cycloaddition in the aqueous medium.