i-Motif folding intermediates with zero-nucleotide loops are trapped by 2'-fluoroarabinocytidine via F···H and O···H hydrogen bonds.

G-quadruplex and i-motif nucleic acid structures are believed to fold through kinetic partitioning mechanisms. Such mechanisms explain the structural heterogeneity of G-quadruplex metastable intermediates which have been extensively reported. On the other hand, i-motif folding is regarded as predictable, and research on alternative i-motif folds is limited.

Structural Polymorphism of Guanine Quadruplex-Containing Regions in Human Promoters.

Intramolecular guanine quadruplexes (G4s) are non-canonical nucleic acid structures formed by four guanine (G)-rich tracts that assemble into a core of stacked planar tetrads. G4-forming DNA sequences are enriched in gene promoters and are implicated in the control of gene expression. Most G4-forming DNA contains more G residues than can simultaneously be incorporated into the core resulting in a variety of different possible G4 structures.

Ion Depletion in the Interfacial Microenvironment from Cell-Surface Interactions.

The nanoscale region immediately adjacent to surfaces, although challenging to probe, is directly responsible for local chemical and physical interactions between a material and its surroundings. Cell-surface contacts are mediated by a combination of electrostatic and acid-base interactions that alter the local environment over time. In this study, a label-free vibrational probe with a nanometer length scale reveals that the electrostatic potential at a silica surface gradually increases in the presence of bacteria in solution.

Using transient equilibria (TREQ) to measure the thermodynamics of slowly assembling supramolecular systems.

Supramolecular chemistry involves the noncovalent assembly of monomers into materials with unique properties and wide-ranging applications. Thermal analysis is a key analytical tool in this field, as it provides quantitative thermodynamic information on both the structural stability and nature of the underlying molecular interactions. However, there exist many supramolecular systems whose kinetics are so slow that the thermodynamic methods currently applied are unreliable or fail completely.

Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL covalent inhibitors.

Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CL non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL.

Tuning DNA Supramolecular Polymers by the Addition of Small, Functionalized Nucleobase Mimics.

Nucleobase mimicking small molecules able to reconfigure DNA are a recently discovered strategy that promises to extend the structural and functional diversity of nucleic acids. However, only simple, unfunctionalized molecules such as cyanuric acid and melamine have so far been used in this approach. In this work, we show that the addition of substituted cyanuric acid molecules can successfully program polyadenine strands to assemble into supramolecular fibers.

EDTA-Gradient Loading of Doxorubicin into Ferrocene-Containing Liposomes: Effect of Lipid Composition and Visualization of Triggered Release by Cryo-TEM.

Efficient delivery of therapeutic compounds to their sites of action has been a ubiquitous concern throughout the history of human medicine. The tumor microenvironment offers a variety of endogenous stimuli that may be exploited by a responsive nanocarrier, including heterogeneities in redox potential. In the early stages of the design of such responsive delivery systems, it is necessary to develop a comprehensive understanding of the biophysical mechanism by which the stimulus response occurs, as well as how the response may change from the inclusion of cargo compounds.

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms.

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures.

Frustrated folding of guanine quadruplexes in telomeric DNA.

Human chromosomes terminate in long, single-stranded, DNA overhangs of the repetitive sequence (TTAGGG)n. Sets of four adjacent TTAGGG repeats can fold into guanine quadruplexes (GQ), four-stranded structures that are implicated in telomere maintenance and cell immortalization and are targets in cancer therapy. Isolated GQs have been studied in detail, however much less is known about folding in long repeat sequences.

Parallel reaction pathways accelerate folding of a guanine quadruplex.

G-quadruplexes (G4s) are four-stranded, guanine-rich nucleic acid structures that can influence a variety of biological processes such as the transcription and translation of genes and DNA replication. In many cases, a single G4-forming nucleic acid sequence can adopt multiple different folded conformations that interconvert on biologically relevant timescales, entropically stabilizing the folded state. The coexistence of different folded conformations also suggests that there are multiple pathways leading from the unfolded to the folded state ensembles, potentially modulating the folding rate and biological activity.

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms.

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure.

Amplified Self-Immolative Release of Small Molecules by Spatial Isolation of Reactive Groups on DNA-Minimal Architectures.

Triggering the release of small molecules in response to unique biomarkers is important for applications in drug delivery and biodetection. Due to low quantities of biomarker, amplifying release is necessary to gain appreciable responses. Nucleic acids have been used for both their biomarker-recognition properties and as stimuli, notably in amplified small-molecule release by nucleic-acid-templated catalysis (NATC).

Conformational Dynamics of Strand Register Shifts in DNA G-Quadruplexes.

The complex folding energy landscape of DNA G-quadruplexes leads to numerous conformations for this functionally important class of noncanonical DNA structures. A new layer of conformational heterogeneity comes from sequences with different numbers of G-nucleotides in each of the DNA G-strands that form the four-stranded G-quartet core. The mechanisms by which G-quadruplexes transition from one folded conformation to another are currently unknown.