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.
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.
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.
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.
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.
A series of isatin derivatives bearing three different substituent groups at the N-1, C-3 and C-5 positions of the isatin scaffold were systematically designed and synthesized to study the ...structure-activity relationship of their inhibition of bacterial peptidoglycan glycosyltransferase (PGT) activity and antimicrobial susceptibility against
S. aureus
,
E. coli
and methicillin-resistant
Staphylococcus aureus
(MRSA (BAA41)) strains. The substituents at these sites are pointing towards three different directions from the isatin scaffold to interact with the amino acid residues in the binding pocket of PGT. Comparative studies of their structure-activity relationship allow us to gain better understanding of the direction of the substituents that contribute critical interactions leading to inhibition activity against the bacterial enzyme. Our results indicate that the modification of these sites is able to maximize the antimicrobial potency and inhibitory action against the bacterial enzyme. Two compounds show good antimicrobial potency (MIC = 3 μg mL
−1
against
S. aureus
and MRSA; 12-24 μg mL
−1
against
E. coli
). Results of the inhibition study against the bacterial enzyme (
E. coli
PBP 1b) reveal that some compounds are able to achieve excellent
in vitro
inhibitions of bacterial enzymatic activity (up to 100%). The best half maximal inhibitory concentration (IC
50
) observed among the new compounds is 8.9 μM.
Isatin-based small molecules targeting bacterial peptidoglycan glycosyltransferase are potent antimicrobial agents against
S. aureus
,
E. coli
and methicillin-resistant
Staphylococcus aureus
strains.
A new electrocatalytic biosensor (MOF-74(Cu) NS-CC) based on the in situ deposition of MOF-74(Cu) nanosheet on carbon cloth via a bottom-up synthetic approach in a glass tube was developed. The ...electrocatalytic activity of the deposited MOF-74(Cu) NS was demonstrated in the oxidation of glucose to gluconate under alkaline conditions. The results revealed that the proposed method of in situ formation of MOF-74(Cu) NS onto a carbon cloth surface in a multi-layer solution is capable to generate a stable MOF-74(Cu) NS-CC electrode with excellent sensing performance. When the as-synthesized MOF-74(Cu) NS-CC was applied directly as the working electrode for glucose sensing, it showed much higher conductivity and redox activity than MOF-74(Cu) NS-GCE. With the potential applied at 0.55 V (vs. Ag/AgCl), this new electrocatalytic biosensor exhibits an excellent linear relationship between current density and concentration of glucose. Moreover, a wide linear range of detection (1.0 to 1000 μM) was observed. The limit of detection was found to be 0.41 μM (S/
N
= 3). The response sensitivity is 3.35 mA mM
−1
cm
−2
when the concentration of glucose is in the range 1–100 μM and 3.81 mA mM
−1
cm
−2
for the 100–1000 μM concentration range. This study provides a low-cost, easy to prepare, and reproducible methodology for the synthesis of highly redox-active nanomaterials based on the in situ formation of two-dimensional MOF-74(Cu) NS for the development of new electrocatalytic biosensors.
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