Destabilizing Interactions in Human Telomeric G-Quadruplex Multimers.

G-Quadruplexes are secondary structures that may form in G-rich nucleic acid sequences. The extended overhang at the ends of human telomeres has the potential to form multiple G-Quadruplexes that are crucial in regulating key biological processes. Here, we employ small-angle X-ray scattering-guided extremely coarse-grained simulations to provide a picture of the arrangement of G-Quadruplexes in long telomeric sequences.

Protective effects of silk fibroin against 6-OHDA in SH-SY5Y human neuroblastoma cells and comparative study with its release from gelatin films.

In this study, we analyzed the neuroprotective action of silk fibroin (SF) regenerated with calcium chloride (CaCl), distinguishing the effects of CaCl and SF, and subsequently fabricating a neuroprotective hybrid material based on SF gelatin film. Cytotoxicity induced by 6-hydroxydopamine (6-OHDA) on the human neuroblastoma SH-SY5Y cell line showed that SF had a significant shielding power against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y neuroblastoma cells, as assessed by the CCK-8 assay, cell imaging and cell cycle using flow cytometer. Specifically, the concurrent treatment with SF and 6-OHDA produced a marked neuroprotective effect.

Black phosphorus/silk fibroin films hamper filamentous and invasive growth of .

The ability of fungi and bacteria to form biofilms on surfaces poses a serious threat to health and a problem in industrial settings. In this work, we investigated how the surface stiffness of silk fibroin (SF) films is modulated by the interaction with black phosphorus (BP) flakes, quantifying the morphogenesis of cells. Raman and infrared (IR) spectroscopies, along with scanning transmission electron microscopy, allowed us to quantify the thickness and diameter of BP flakes dispersed in the SF matrix (, 5.

Hindered intermolecular stacking of anti-parallel telomeric G-quadruplexes.

Telomeric G-quadruplexes (G4s) are non-canonical DNA structures composed of TTAGGG repeats. They are extensively studied both as biomolecules key for genome stability and as promising building blocks and functional elements in synthetic biology and nanotechnology. This is why it is extremely important to understand how the interaction between G4s is affected by their topology.

Development of Ultraviolet-Shielding Bamboo/Silk Fibroin Hybrid Films with Good Mechanical Properties: A Proof Study on Human Keratinocyte Cells.

In this study, we report the preparation and characterization of water-stable films with UV-shielding and good mechanical properties, exploiting the synergistic effect of regenerated silk fibroin and bamboo-derived cellulose. Silk fibroin (SF)/bamboo (B) hybrid films are achieved by solubilizing both silk and bamboo fibers in formic acid with added CaCl. Infrared spectroscopy indicates that SF, when combined with bamboo, undergoes a conformational transition, providing evidence of an increase in SF crystallinity.

Conformational transitions in redissolved silk fibroin films and application for printable self-powered multistate resistive memory biomaterials.

3D printing of water stable proteins with elastic properties offers a broad range of applications including self-powered biomedical devices driven by piezoelectric biomaterials. Here, we present a study on water-soluble silk fibroin (SF) films. These films were prepared by mixing degummed silk fibers and calcium chloride (CaCl) in formic acid, resulting in a silk I-like conformation, which was then converted into silk II by redissolving in phosphate buffer (PBS).

Molecular mechanisms behind BRACO19 and human telomeric G-quadruplex interaction.

Human telomeres (HTs) can form DNA G-quadruplex (G4), an attractive target for anticancer and antiviral drugs. HT-G4s exhibit inherent structural polymorphism, posing challenges for understanding their specific recognition by ligands. Here, we aim to explore the impact of different topologies within a small segment of the HT (Tel22) on its interaction with BRACO19, a rationally designed G4 ligand with high quadruplex affinity, already employed in in-vivo treatments.

Dynamic Personality of Proteins and Effect of the Molecular Environment.

Protein dynamics display distinct traits that are linked to their specific biological function. However, the interplay between intrinsic dynamics and the molecular environment on protein stability remains poorly understood. In this study, we investigate, by incoherent neutron scattering, the subnanosecond time scale dynamics of three model proteins: the mesophilic lysozyme, the thermophilic thermolysin, and the intrinsically disordered β-casein.

Stacking Interactions and Flexibility of Human Telomeric Multimers.

G-quadruplexes (G4s) are helical four-stranded structures forming from guanine-rich nucleic acid sequences, which are thought to play a role in cancer development and malignant transformation. Most current studies focus on G4 monomers, yet under suitable and biologically relevant conditions, G4s undergo multimerization. Here, we investigate the stacking interactions and structural features of telomeric G4 multimers by means of a novel low-resolution structural approach that combines small-angle X-ray scattering (SAXS) with extremely coarse-grained (ECG) simulations.

Stability of Human Telomeric G-Quadruplexes Complexed with Photosensitive Ligands and Irradiated with Visible Light.

Guanine-rich DNA sequences can fold into non-canonical nucleic acid structures called G-quadruplexes (G4s). These nanostructures have strong implications in many fields, from medical science to bottom-up nanotechnologies. As a result, ligands interacting with G4s have attracted great attention as candidates in medical therapies, molecular probe applications, and biosensing.

Stabilization of the Dimeric State of SARS-CoV-2 Main Protease by GC376 and Nirmatrelvir.

The main protease (Mpro or 3CLpro) is an enzyme that is evolutionarily conserved among different genera of coronaviruses. As it is essential for processing and maturing viral polyproteins, Mpro has been identified as a promising target for the development of broad-spectrum drugs against coronaviruses. Like SARS-CoV and MERS-CoV, the mature and active form of SARS-CoV-2 Mpro is a dimer composed of identical subunits, each with a single active site.

Polymorphism and Ligand Binding Modulate Fast Dynamics of Human Telomeric G-Quadruplexes.

Telomeric G-quadruplexes (G4s) are promising targets in the design and development of anticancer drugs. Their actual topology depends on several factors, resulting in structural polymorphism. In this study, we investigate how the fast dynamics of the telomeric sequence AG3(TTAG3)3 (Tel22) depends on the conformation.

Role of fast dynamics in the complexation of G-quadruplexes with small molecules.

G-quadruplexes (G4s) formed by the human telomeric sequence AG (TTAG) (Tel22) play a key role in cancer and aging. We combined elastic incoherent neutron scattering (EINS) and quasielastic incoherent neutron scattering (QENS) to characterize the internal dynamics of Tel22 G4s and to assess how it is affected by complexation with two standard ligands, Berberine and BRACO19. We show that the interaction with the two ligands induces an increase of the overall mobility of Tel22 as quantified by the mean squared displacements (MSD) of hydrogen atoms.

The Combination of Molnupiravir with Nirmatrelvir or GC376 Has a Synergic Role in the Inhibition of SARS-CoV-2 Replication In Vitro.

Introduction: The development of effective vaccines has partially mitigated the trend of the SARS-CoV-2 pandemic; however, the need for orally administered antiviral drugs persists. This study aims to investigate the activity of molnupiravir in combination with nirmatrelvir or GC376 on SARS-CoV-2 to verify the synergistic effect. Methods: The SARS-CoV-2 strains 20A.

Solvent Vibrations as a Proxy of the Telomere G-Quadruplex Rearrangements across Thermal Unfolding.

G-quadruplexes (G4s) are noncanonical forms of DNA involved in many key genome functions. Here, we exploited UV Resonance Raman scattering to simultaneously explore the vibrational behavior of a human telomeric G4 (Tel22) and its aqueous solvent as the biomolecule underwent thermal melting. We found that the OH stretching band, related to the local hydrogen-bonded network of a water molecule, was in strict relation with the vibrational features of the G4 structure as a function of temperature.

Porphyrin Binding and Irradiation Promote G-Quadruplex DNA Dimeric Structure.

Nucleic acid sequences rich in guanines can organize into noncanonical DNA G-quadruplexes (G4s) of variable size. The design of small molecules stabilizing the structure of G4s is a rapidly growing area for the development of novel anticancer therapeutic strategies and bottom-up nanotechnologies. Among a multitude of binders, porphyrins are very attractive due to their light activation that can make them valuable conformational regulators of G4s.