Molecular nanoarchitectonics of proton triggered tetraphenylethylene-based detector: colorimetric, reversible, and intracellular pH.

In this paper, we designed, synthesized, and characterized 4,4',4'',4'''-(ethene-1,1,2,2-tetrayl)tetrakis(,-dimethylaniline) (1). Furthermore, UV-Vis absorbance and fluorescence emission studies reveal that 1 acts as a selective and sensitive probe for reversible acid-base sensing in solution as well as in the solid state. Nevertheless, the probe exhibited colorimetric sensing and intracellular fluorescent cell imaging of acid-base sensitive cells, making it a practical sensor with several potential applications in chemistry.

Revisiting recent unusual drug-DNA complex structures: Implications for cancer and neurological disease diagnostics and therapeutics.

DNA plays a crucial role in various biological processes such as protein production, replication, recombination etc. by adopting different conformations. Targeting these conformations by small molecules is not only important for disease therapy, but also improves our understanding of the mechanisms of disease development.

Alternative RNA Conformations: Companion or Combatant.

RNA molecules, in one form or another, are involved in almost all aspects of cell physiology, as well as in disease development. The diversity of the functional roles of RNA comes from its intrinsic ability to adopt complex secondary and tertiary structures, rivaling the diversity of proteins. The RNA molecules form dynamic ensembles of many interconverting conformations at a timescale of seconds, which is a key for understanding how they execute their cellular functions.

Aminoglycoside antibiotic kanamycin functionalized tetraphenylethylene molecular probe for highly selective detection of bovine serum albumin protein.

A novel tetraphenylethylene (TPE) functionalized aminoglycoside antibiotic kanamycin (TPE-kana 1) has been successfully synthesized and characterized by means of modern analytical and spectroscopic techniques. The probe TPE-kana 1 showed strong affinity towards bovine serum albumin (BSA) compared to its other biological competitors. The recognition of BSA have been investigated employing UV-Vis absorption and fluorescence emission spectroscopy.

Tetraphenylethene Derivatives Modulate the RNA Hairpin-G-Quadruplex Conformational Equilibria in Proto-oncogenes.

RNA G-quadruplex (GQs) sequences in 5'-UTRs of certain proto-oncogenes co-localize with hairpin (Hp) forming sequences resulting in intramolecular Hp-GQ conformational equilibria, which is suggested to regulate cancer development and progression. Thus, regulation of Hp-GQ equilibria with small molecules is an attractive but less explored therapeutic approach. Herein, two tetraphenylethene (TPE) derivatives, TPE-Py and TPE-MePy, were synthesized and their effect on Hp-GQ equilibrium was explored.

From bench side to clinic: Potential and challenges of RNA vaccines and therapeutics in infectious diseases.

The functional and structural versatility of Ribonucleic acids (RNAs) makes them ideal candidates for overcoming the limitations imposed by small molecule-based drugs. Hence, RNA-based biopharmaceuticals such as messenger RNA (mRNA) vaccines, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNA mimics, anti-miRNA oligonucleotides (AMOs), aptamers, riboswitches, and CRISPR-Cas9 are emerging as vital tools for the treatment and prophylaxis of many infectious diseases. Some of the major challenges to overcome in the area of RNA-based therapeutics have been the instability of single-stranded RNAs, delivery to the diseased cell, and immunogenicity.

Synthesis and evaluation of antimycobacterial activity of riboflavin derivatives.

The riboflavin biosynthetic pathway is a promising target for the development of novel antimycobacterial drugs given the lack of riboflavin transporter in M. tuberculosis. Herein, a series of riboflavin derivatives was designed, synthesized and screened for their antimycobacterial and antibacterial activity.

Crowding Shifts the FMN Recognition Mechanism of Riboswitch Aptamer from Conformational Selection to Induced Fit.

In bacteria, the binding between the riboswitch aptamer domain and ligand is regulated by environmental cues, such as low Mg in macrophages during pathogenesis to ensure spatiotemporal expression of virulence genes. Binding was investigated between the flavin mononucleotide (FMN) riboswitch aptamer and its anionic ligand in the presence of molecular crowding agent without Mg ion, which mimics pathogenic conditions. Structural, kinetic, and thermodynamic analyses under the crowding revealed more dynamic conformational rearrangements of the FMN riboswitch aptamer compared to dilute Mg -containing solution.

tRNA Shifts the G-quadruplex-Hairpin Conformational Equilibrium in RNA towards the Hairpin Conformer.

Non-coding RNAs play important roles in cellular homeostasis and are involved in many human diseases including cancer. Intermolecular RNA-RNA interactions are the basis for the diverse functions of many non-coding RNAs. Herein, we show how the presence of tRNA influences the equilibrium between hairpin and G-quadruplex conformations in the 5' untranslated regions of oncogenes and model sequences.

Real-Time Monitoring of G-Quadruplex Formation during Transcription.

Cotranscriptional folding of an RNA transcript enables formation of metastable RNA structures. Thermodynamic and kinetic properties of RNA G-quadruplex formation have previously been investigated using purified guanine-rich oligonucleotides. Here, we describe a method for analysis of cotranscriptional dynamics of the G-quadruplex formation based on real-time monitoring of the fluorescence of G-quadruplex ligands.

Tuning riboswitch-mediated gene regulation by rational control of aptamer ligand binding properties.

Riboswitch-mediated control of gene expression depends on ligand binding properties (kinetics and affinity) of its aptamer domain. A detailed analysis of interior regions of the aptamer, which affect the ligand binding properties, is important for both understanding natural riboswitch functions and for enabling rational design of tuneable artificial riboswitches. Kinetic analyses of binding reaction between flavin mononucleotide (FMN) and several natural and mutant aptamer domains of FMN-specific riboswitches were performed.

Real-time monitoring of DNA hybridization kinetics on living cell surfaces.

We determined hybridization rates of DNA probes bound to the surfaces of a human cell, and compared the rates with those determined in solution. The rates were slower on the cell surface than in solution-phase. The position of the nucleation site but not the location of the formed duplex relative to the cell surface adversely affected the hybridization kinetics.

5-Phenylselenyl- and 5-methylselenyl-methyl-2'-deoxyuridine induce oxidative stress, DNA damage, and caspase-2-dependent apoptosis in cancer cells.

In the present study, we investigated the signaling pathways implicated in the induction of apoptosis by two modified nucleosides, 5-phenylselenyl-methyl-2'-deoxyuridine (PhSe-T) and 5-methylselenyl-methyl-2'-deoxyuridine (MeSe-T), using human cancer cell lines. The induction of apoptosis was associated with proteolytic activation of caspase-3 and -9, PARP cleavage, and decreased levels of IAP family members, including c-IAP-1 and c-IAP-2, but had no effect on XIAP and survivin. PhSe-T and MeSe-T also enhanced the activities of caspase-2 and -8, Bid cleavage, and the conformational activation of Bax.

Potent radiosensitizing agents: 5-methylselenyl- and 5-phenylselenyl-methyl-2'-deoxyuridine.

This Letter describes the novel radiosensitizing agents based on nucleoside base modification. In addition to the known 5-phenylselenide derivative, 5-methylselenide modified thymidine, which has a van der Waals radius smaller than the phenyl group, was newly synthesized. The similar monomer activity of 5-methylselenide derivative under oxidation condition was confirmed by NMR experiments.