The development of site‐specific, target‐selective and biocompatible small molecule ligands as a fluorescent tool for real‐time study of cellular functions of RNA G‐quadruplexes (G4s), which are ...associated with human cancers, is of significance in cancer biology. We report a fluorescent ligand that is a cytoplasm‐specific and RNA G4‐selective fluorescent biosensor in live HeLa cells. The in vitro results show that the ligand is highly selective targeting RNA G4s including VEGF, NRAS, BCL2 and TERRA. These G4s are recognized as human cancer hallmarks. Moreover, intracellular competition studies with BRACO19 and PDS, and the colocalization study with G4‐specific antibody (BG4) in HeLa cells may support that the ligand selectively binds to G4s in cellulo. Furthermore, the ligand was demonstrated for the first time in the visualization and monitoring of dynamic resolving process of RNA G4s by the overexpressed RFP‐tagged DHX36 helicase in live HeLa cells.
A fluorescent ligand is designed as a cytoplasm‐specific probe targeting RNA G4s including VEGF, NRAS and BCL2 in live cancer cells. The ligand is demonstrated for the first time in real‐time visualization of RNA G4‐resolving process with the overexpressed RFP‐tagged DHX36 helicase in live HeLa cells and could be a nontoxic and highly selective fluorescent tool for the study of RNA G4s of cancer hallmarks at low concentration for their cancer biology in live human cells.
The design and synthesis of multifunctional chitosan hydrogels based on polymerized ionic liquid and a near-infrared (NIR) fluorescent probe (PIL-CS) is a promising strategy, which not only prevents ...the transition from acute to chronic wounds, but also provides prompt measures regarding microenvironmental alterations in chronic wounds. PIL-CS hydrogel can real-time visualize wound pH through in vivo NIR fluorescent imaging and also feature the pH-responsive sustained drug release, such as antioxidant, to eliminate reactive oxygen species (ROS) and to boost diabetic wound healing. PIL-CS hydrogel is specific, sensitive, stable, and reversible in response to pH changes at the wound site. It, therefore, enables real-time monitoring for a dynamic pH change in the microenvironment of irregular wounds. PIL-CS hydrogel is also designed to possess many merits including high water containment and swelling rate, good biocompatibility, electrical conductivity, antifreeze, tissue adhesion, hemostatic performance, and efficient antibacterial activity against MRSA. In vivo studies showed that PIL-CS hydrogel provided fast diabetic wound healing support, promoted vascular endothelial growth factor (VEGF) production, and reduced ROS and tumor necrosis factor (TNF-α) generation. The results support that the hydrogels coupled with NIR fluorescent probes can be an excellent diabetic wound dressing for enhancing and real-time monitoring skin restoration and regeneration.
β‐1,3‐D‐glucan has been reported to have a series of bioactivities including antitumor, antimicrobial, anti‐inflammatory and antioxidative effects; however, its insolubility in neutral aqueous ...solution significantly restricts the potential application in biological and medicine fields. Herein, a water‐soluble aminated β‐1,3‐D‐glucan (AG) was synthesized and the anti‐inflammatory effect, cytotoxicity and plasmid DNA (pDNA) binding capacity of AG, serum stability, the particle sizes and zeta potentials of AG/pDNA nanocomposites, and the transfection efficiency and mechanism of action were studied. AG shows no obvious cytotoxicity within the range of working concentration (1–64 μg/ml) and it exerts potent anti‐inflammatory effect independent on Dectin‐1 and TLR2. AG/pDNA nanocomposites prepared by electrostatic interaction possess an appropriate particle size ranged from 192.8 to 118.4 nm and zeta potentials ranged from 20.880 to 27.16 mV with the N/P ratios from 5 to 100. AG/pDNA nanocomposites at the N/P ratios of 10 and 20 were able to show superior transfection efficiencies in RAW 264.7 cells as a result of their suitable particle size, zeta potential, anti‐inflammatory effect, and the specific interaction with pattern recognition receptors (Dectin‐1 and TLR2). These results indicate that AG is a potential candidate for DNA delivery system due to its potent anti‐inflammatory effect and high transfection efficiency.
No destaining required: The luminescence properties of an iridium(III)–2‐phenylpyridine complex can be utilized for the detection of proteins in sodium dodecyl sulfate–polyacrylamide gels. Emissive ...gel images obtained upon staining with the complex are visible under UV light. The high detection sensitivity for histidine‐rich proteins (right vial, compared to a non‐histidine‐tagged protein) suggests potential applications in the signaling of biomolecules.
The formation of G-quadruplex structures (G4s)
from guanine (G)-rich nucleic acid sequences of DNA and RNA stabilized with monovalent cations, typically K
and Na
, under physiological conditions, has ...been verified experimentally and some of them have high-resolution NMR or
-ray crystal structures; however, the biofunction of these special noncanonical secondary structures of nucleic acids has not been fully understood and their existence
is still controversial at present. It is generally believed that the folding and unfolding of G4s
is a transient process. Accumulating evidence has shown that G4s may play a role in the regulation of certain important cellular functions including telomere maintenance, replication, transcription and translation. Therefore, both DNA and RNA G4s of human cancer hallmark genes are recognized as the potential anticancer drug target for the investigation in cancer biology, chemical biology and drug discovery. The relationship between the sequence, structure and stability of G4s, the interaction of G4s with small molecules, and insights into the rational design of G4-selective binding ligands have been intensively studied over the decade. At present, some G4-ligands have achieved a new milestone and successfully entered the human clinical trials for anticancer therapy. Over the past few decades, numerous efforts have been devoted to anticancer therapy; however, G4s for molecular recognition and live cell imaging and for application as antibacterial agents and antibiofilms against antibiotic resistance have been obviously underexplored. The recent advances in G4-ligands in these areas are thus selected and discussed concentratedly in this article in order to shed light on the emerging role of G4s in chemical biology and therapeutic prospects against bacterial infections. In addition, the recently published molecular scaffolds for designing small ligands selectively targeting G4s in live cell imaging, bacterial biofilm imaging, and antibacterial studies are discussed. Furthermore, a number of underexplored G4-targets from the cytoplasmic membrane-associated DNA, the conserved promoter region of
genomes, the RNA G4-sites in the transcriptome of
and
, and the mRNA G4-sites in the sequence for coding the vital bacterial FtsZ protein are highlighted to further explore in G4-drug development against human diseases.
Abstract
RNA structures, including those formed from coding and noncoding RNAs, alternative to protein‐based drug targets, could be a promising target of small molecules for drug discovery against ...various human diseases, particularly in anticancer, antibacterial and antivirus development. The normal cellular activity of cells is critically dependent on the function of various RNA molecules generated from DNA transcription. Moreover, many studies support that mRNA‐targeting small molecules may regulate the synthesis of disease‐related proteins via the non‐covalent mRNA‐ligand interactions that do not involve gene modification. RNA‐ligand interaction is thus an attractive approach to address the challenge of “undruggable” proteins in drug discovery because the intracellular activity of these proteins is hard to be suppressed with small molecule ligands. We selectively surveyed a specific area of RNA structure‐selective small molecule ligands in fluorescence live cell imaging and drug discovery because the area was currently underexplored. This state‐of‐the‐art review thus mainly focuses on the research published within the past three years and aims to provide the most recent information on this research area; hopefully, it could be complementary to the previously reported reviews and give new insights into the future development on RNA‐specific small molecule ligands for live cell imaging and drug discovery.
A smart and heavy-atom-free photoinactive nano-photosensitizer capable of being activated by cysteine at the tumor site to generate highly photoactive nano-photosensitizers that show strong NIR ...absorption and fluorescence with a good singlet oxygen quantum yield (16.8%) for photodynamic therapy is reported.
In the present study, a novel polysaccharide (THDP-3) purified from cane leaves of Tetrastigma hemsleyanum Diels et Gilg was obtained via anion exchange chromatography and the structural analyses of ...the compound indicated that THDP-3 is a homogenous polysaccharide with molecular weight of 77.98 kDa. Our results show that it consists of rhamnose, arabinose, mannose, glucose and galactose at molar ratio of 1.0: 1.3: 2.5: 2.3:3.1 with main backbones of →4)-α-D-GalAp-(1→, →4)-β-D-Galp-(1→ and →4)-α-D-Glcp-(1→, and main branches of β-D-Manp-(1→, →3,6-β-D-Manp-1→ and α-D-Araf-(1→. In the anti-diabetic assays, THDP-3 showed significant hypoglycemic activity in alloxan-induced diabetic mice. In addition, THDP-3 was found regulating the expression of glucokinase, amp-activated protein kinase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. These new findings indicate the high potential in therapeutic mechanisms investigation using THDP-3. Moreover, our results of hypoglycemic activity using THDP-3 demonstrated that the compound could serve as a potential anti-diabetic agent.
•A novel polysaccharide was isolated from Tetrastigma hemsleyanum Diels et Gilg.•The chemical structure of THDP-3 was characterized.•THDP-3 exhibited hypoglycemic effects in alloxan-induced diabetic mice.•The underlying mechanisms were elucidated.
A large number of studies have shown that matrine (
) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and ...application. Fifty-eight
derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds
,
,
,
,
,
,
,
, and
showed good larvicidal activity against
, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC
values of
,
, and
reached 147.65, 140.08, and 205.79 μg/mL, respectively, whereas the LC
value of
was 659.34 μg/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The
derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds
and
exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 μg/mL, whereas the inhibitory rate of
was 9.88%. Therefore, the structural modification and mosquitocidal activity of
and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin.
