Nucleotide-decorated AuNPs as probes for nucleotide-binding proteins

Gold nanoparticles (AuNPs) decorated with biologically relevant molecules have variety of applications in optical sensing of bioanalytes. Coating AuNPs with small nucleotides produces particles with high stability in water, but functionality-compatible strategies are needed to uncover the full potential of this type of conjugates. Here, we demonstrate that lipoic acid-modified dinucleotides can be used to modify AuNPs surfaces in a controllable manner to produce conjugates that are stable in aqueous buffers and biological mixtures and capable of interacting with nucleotide-binding proteins. Using this strategy we obtained AuNPs decorated with 7-methylguanosine mRNA 5’ cap analogs and showed that they bind cap-specific protein, eIF4E. AuNPs decorated with non-functional dinucleotides also interacted with eIF4E, albeit with lower affinity, suggesting that eIF4E binding to cap-decorated AuNPs is partially mediated by unspecific ionic interactions. This issue was overcome by applying lipoic-acid-Tris conjugate as a charge-neutral diluting molecule. Tris-Lipo-diluted cap-AuNPs conjugates interacted with eIF4E in fully specific manner, enabling design of functional tools. To demonstrate the potential of these conjugates in protein sensing, we designed a two-component eIF4E sensing system consisting of cap-AuNP and 4E-BP1-AuNP conjugates, wherein 4E-BP1 is a short peptide derived from 4E-BP protein that specifically binds eIF4E at a site different to that of the 5’ cap. This system facilitated controlled aggregation, in which eIF4E plays the role of the agent that crosslinks two types of AuNP, thereby inducing a naked-eye visible absorbance redshift. The reported AuNPs-nucleotide conjugation method based on lipoic acid affinity for gold, can be harnessed to obtain other types of nucleotide-functionalized AuNPs, thereby paving the way to studying other nucleotide-binding proteins.

Extracellular Vesicles as a Means of Viral Immune Evasion, CNS Invasion, and Glia-Induced Neurodegeneration

Extracellular vesicles (EVs) are small, membrane-bound vesicles released by cells as a means of intercellular communication. EVs transfer proteins, nucleic acids, and other biologically relevant molecules from one cell to another. In the context of viral infections, EVs can also contain viruses, viral proteins, and viral nucleic acids. While there is some evidence that the inclusion of viral components within EVs may be part of the host defense, much of the research in this field supports a pro-viral role for EVs. Packaging of viruses within EVs has repeatedly been shown to protect viruses from antibody neutralization while also allowing for their integration into cells otherwise impervious to the virus. EVs also bidirectionally cross the blood-brain barrier (BBB), providing a potential route for peripheral viruses to enter the brain while exiting EVs may serve as valuable biomarkers of neurological disease burden. Within the brain, EVs can alter glial activity, increase neuroinflammation, and induce neurotoxicity. The purpose of this mini-review is to summarize research related to viral manipulation of EV-mediated intercellular communication and how such manipulation may lead to infection of the central nervous system, chronic neuroinflammation, and neurodegeneration.

Proteomic Profiling of Ectosomes Derived from Paired Urothelial Bladder Cancer and Normal Cells Reveals the Presence of Biologically-Relevant Molecules

Protein content of extracellular vesicles (EVs) can modulate different processes during carcinogenesis. Novel proteomic strategies have been applied several times to profile proteins present in exosomes released by urothelial bladder cancer (UBC) cells. However, similar studies have not been conducted so far on another population of EVs, i.e., ectosomes. In the present study we used a shotgun nanoLC–MS/MS proteomic approach to investigate the protein content of ectosomes released in vitro by T-24 UBC cells and HCV-29 normal ureter epithelial cells. In addition, cancer-promoting effects exerted by UBC-derived ectosomes on non-invasive cells in terms of cell proliferation and migratory properties were assessed. In total, 1158 proteins were identified in T-24-derived ectosomes, while HCV-29-derived ectosomes contained a lower number of 259 identified proteins. Qualitative analysis revealed 938 proteins present uniquely in T-24-derived ectosomes, suggesting their potential applications in bladder cancer management as diagnostic and prognostic biomarkers. In addition, T-24-derived ectosomes increased proliferation and motility of recipient cells, likely due to the ectosomal transfer of the identified cancer-promoting molecules. The present study provided a focused identification of biologically relevant proteins in UBC-derived ectosomes, confirming their role in UBC development and progression, and their applicability for further biomarker-oriented studies in preclinical or clinical settings.

Multi-component reactions for the synthesis of biologically relevant molecules under environmentally benign conditions

: Heterocycles are the most important skeleton as they are biologically and medicinally significant. Various chemical methods have been utilized for their synthesis. Among them, environmentally benign condition are most important as they produce less toxic waste and requires less toxic solvents and reagents. There is various literature available on sustainable and multicomponent synthetic. However, it is difficult for the researcher to keep up with the research. Therefore, a review article in the sustainable and multicomponent synthesis of heterocycle was highly required. Herein, we have compiled the literature related to multicomponent reaction under solvent-free conditions, ultrasound-assisted, water or ionic liquid mediated conditions.

Effect of Biologically-Relevant Molecules on the Physico-Chemical Properties of Amorphous Magnesium–Calcium Phosphate Nanoparticles

The recently-discovered endogenous formation of amorphous magnesium–calcium phosphate nanoparticles (AMCPs) in human distal small intestine occurs in a complex environment, which is rich in biologically-relevant molecules and macromolecules that can shape the properties and the stability of these inorganic particles. In this work, we selected as case studies four diverse molecules, which have different properties and are representative of intestinal luminal components, namely butyric acid, lactose, gluten and peptidoglycan. We prepared AMCPs in the presence of these four additives and we investigated their effect on the features of the particles in terms of morphology, porosity, chemical nature and incorporation/adsorption. The combined use of electron microscopy, infrared spectroscopy and thermal analysis showed that while the morphology and microstructure of the particles do not depend on the type of additive present during the synthesis, AMCPs are able to incorporate a significant amount of peptidoglycan, similarly to the process in which they are involved in vivo.

Recent advances in the use of Langmuir monolayers as cell membrane models

Understanding the role of biomolecules in cells at the molecular level has been the trade of Prof. Marcio Francisco Colombo and Prof. Jo�o Ruggiero Neto in their carriers, which is why it was found appropriate to address the use of Langmuir monolayers as cell membrane models in this special issue. In the review paper, we elaborate upon the reasons why Langmuir monolayers are good models with the possible control of membrane composition and molecular packing. After describing several experimental methods to characterize the Langmuir monolayers, we discuss selected results from the last five years where monolayers were made to interact with pharmaceutical drugs, emerging pollutants and other biologically-relevant molecules. The challenges to take the field forward are also commented upon.

Diselenides and Selenocyanates as Versatile Precursors for the Synthesis of Pharmaceutically Relevant Compounds

: Organoselenium chemistry has undergone extensive development during the past decades, mostly due to the unique chemical properties of organoselenium compounds that have been widely explored in a number of synthetic transformations, as well as due to the interesting biological properties of these compounds. Diselenides and selenocyanates constitute the promising classes of organoselenium compounds that possess interesting biological effects and that can be used in the preparation of other selenium compounds. The combination of diselenide and selenocyanate moieties with other biologically relevant molecules (such as heterocycles, steroids, etc.) is a way for the development of compounds with promising pharmaceutical potential. Therefore, the aim of this review is to highlight the recent achievements in the use of diselenides or selenocyanates as precursors for the synthesis of pharmaceutically relevant compounds, preferentially compounds with antitumor and antimicrobial activities.

One-flow synthesis of tetrahydrocannabinol and cannabidiol using homo- and heterogeneous Lewis acids

Continuous flow chemistry holds great potential for the production of biologically relevant molecules. Herein, we present an approach for the continuous synthesis of cannabidiol and tetrahydrocannabinol in a one-flow system. The designed route consists of a reaction cascade involving Friedel-Crafts alkylation, subsequent ring opening and cyclisation in up to 45% yield. The reactions were successfully performed using both hetero- and homogeneous Lewis acids in continuous flow and provide yields that are similar to comparable batch processes. Graphical abstract

The contribution of metalloporphyrin complexes in molecular sensing and in sustainable polymerization processes: a new and unique perspective.

This review highlights the recent developments in the field of metalloporphyrins as optical probes for biologically relevant molecules, such as nitric oxide (NO) and hydrogen sulfide (H2S), and as catalysts...

Graphene field-effect transistors as bioanalytical sensors: design, operation and performance

Changes in the electrical conductance of graphene field-effect transistors (GFETs) are used to perform quantitative analyses of biologically-relevant molecules such as DNA, proteins, ions and small molecules.