ABSTRACT
The design of artificially engineered chiral structures has received much attention, but the implementation of dynamic functions to modulate the chiroptical response of the systems is less explored. Here, we present a light-responsive G-quadruplex (G4)-based assembly in which chirality enrichment is induced, tuned, and fueled by molecular switches. In particular, the mirror-image dependence on photoactivated azo molecules, undergoing trans-to-cis isomerization, shows chiral recognition effects on the inherent flexibility and conformational diversity of DNA G4s having distinct handedness (right- and left-handed). Through a detailed experimental and computational analysis, we bring compelling evidence on the binding mode of the photochromes on G4s, and we rationalize the origin of the chirality effect that is associated with the complexation event.
Subject(s)
Fluorescent Dyes/chemistry , G-Quadruplexes , Light , Circular Dichroism , Nucleic Acid Conformation , Stereoisomerism , Stilbenes/chemistryABSTRACT
Dark nπ* states were shown to have substantial contribution to the destructive photochemistry of pyrimidine nucleobases. Based on quantum-chemical calculations, we demonstrate that the characteristic hydrogen bonding pattern of the GC base pair could facilitate the formation of a wobble excited-state charge-transfer complex. This entails a barrierless electron-driven proton transfer (EDPT) process which enables damageless photodeactivation of the base pair. These photostabilizing properties are retained even when guanine is exchanged to hypoxanthine. The inaccessibility of this process in the AT base pair sheds further light on the reasons why cytosine is less susceptible to the formation of photodimers in double-stranded DNA.
Subject(s)
Base Pairing , DNA/chemistry , Protons , Base Pairing/radiation effects , DNA/genetics , DNA/radiation effects , Hydrogen Bonding , Models, Chemical , Nucleic Acid Conformation , Purinones/chemistry , Pyrimidinones/chemistry , Quantum Theory , Ultraviolet RaysABSTRACT
Faced with the worldwide spread of multidrug-resistant (MDR) bacterial strains, together with a lack of any appropriate treatment, urgent steps to combat infectious diseases should be taken. Usually, bacterial components are studied to understand, by analogy, the functioning of human proteins. However, molecular data from bacteria gathered over the past decades provide a sound basis for the search for novel approaches in medical care. With this current work, we want to direct attention to inhibition of the vSGLT glucose transporter from Vibrio parahaemolyticus belonging to the sodium solute symporter (SSS) family, to block sugar transport into the bacterial cell and, as a consequence, to limit its growth. Potential bacteriostatic properties can be drawn from commercially available drugs developed for human diseases. This goal can also be reached with natural components from traditional herbal medicine. The presented data from the numerical analysis of 44 known inhibitors of sodium glucose symporters shed light on potential novel approaches in fighting Gram-negative multidrug-resistant microorganisms. Graphical abstract Molecular view on vSGLT channel inhibition by gneyulin B, the compound of natural origin.
Subject(s)
Models, Molecular , Quantitative Structure-Activity Relationship , Sodium-Glucose Transport Proteins/chemistry , Stilbenes/chemistry , Antisepsis/methods , Binding Sites , Drug Resistance, Multiple, Bacterial/drug effects , Gram-Negative Bacteria/drug effects , Humans , Ligands , Protein Binding , Protein Conformation , Sodium-Glucose Transport Proteins/antagonists & inhibitors , Stilbenes/pharmacology , Vibrio parahaemolyticus/metabolismABSTRACT
Two endothelial cell lines were selected as models to investigate an effect of incubation with cytokine tumor necrosis factor type α (TNF-α) using Fourier transform infrared (FT-IR) imaging spectroscopy. Both cell lines are often used in laboratories and are typical lung vascular endothelial cells (HMLVEC) derived from the fusion of umbilical vein endothelial cells with lung adenocarcinoma cells (EA.hy926). This study was focused on alteration of spectral changes accompanying inflammation at the cellular level by applying two resolution systems of FT-IR microscopy. The standard approach, with a pixel size of ca. 5.5 µm2, determined the inflammatory state of the whole cell, while a high-magnification resolution (pixel size of ca. 1.1 µm2) provided information at the subcellular level. Importantly, the analysis of IR spectra recorded with different modes produced similar results overall and yielded unambiguous classification of inflamed cells. Generally, the most significant changes in the cells under the influence of TNF-α are related with lipids-their composition and concentration; however, segregation of cells into subcellular compartments provided an additional insight into proteins and nucleic acids related events. The observed spectral alterations are specific for the type of endothelial cell line.
