Infectious diseases are the leading cause of mortality worldwide, with viruses in particular making global impact on healthcare and socioeconomic development. In addition, the rapid development of drug resistance to currently available therapies and adverse side effects due to prolonged use is a serious public health concern. The development of novel treatment strategies is therefore required. The interaction of nanostructures with microorganisms is fast-revolutionizing the biomedical field by offering advantages in both diagnostic and therapeutic applications. Nanoparticles offer unique physical properties that have associated benefits for drug delivery. These are predominantly due to the particle size (which affects bioavailability and circulation time), large surface area to volume ratio (enhanced solubility compared to larger particles), tunable surface charge of the particle with the possibility of encapsulation, and large drug payloads that can be accommodated. These properties, which are unlike bulk materials of the same compositions, make nanoparticulate drug delivery systems ideal candidates to explore in order to achieve and/or improve therapeutic effects. This review presents a broad overview of the application of nanosized materials for the treatment of common viral infections.
Antimicrobial peptides (AMPs) are a heterogeneous class of compounds found in a variety of organisms including humans and, so far, hundreds of these structures have been isolated and characterised. They can be described as natural microbicide, selectively cytotoxic to bacteria, whilst showing minimal cytotoxicity towards the mammalian cells of the host organism. They act by their relatively strong electrostatic attraction to the negatively charged bacterial cells and a relatively weak interaction to the eukaryote host cells. The ability of these peptides to accumulate at sites of infection combined with the minimal host's cytotoxicity motivated for this review to highlight the role and the usefulness of AMPs for PET with emphasis on their mechanism of action and the different interactions with the bacterial cell. These details are key information for their selective properties. We also describe the strategy, design, and utilization of these peptides as potential radiopharmaceuticals as their combination with nuclear medicine modalities such as SPECT or PET would allow noninvasive whole-body examination for detection of occult infection causing, for example, fever of unknown origin.
The first synthesis and biological activity of a teixobactin analogue is reported. Substitution of the unusual L-allo-enduracididine residue by the naturally occurring L-arginine was achieved, and the analogue gave an activity trend similar to that of teixobactin (against Gram-postive bacteria) and meropenem, which was approved by the FDA in 1996. The synthetic route used allows for the synthesis of the natural product as well as the development of a program of medicinal chemistry.
The glycocalyx surrounds every eukaryotic cell and is a complex mesh of proteins and carbohydrates. It consists of proteoglycans with glycosaminoglycan side chains, which are highly sulfated under normal physiological conditions. The degree of sulfation and the position of the sulfate groups mainly determine biological function. The intact highly sulfated glycocalyx of the epithelium may repel severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) through electrostatic forces. However, if the glycocalyx is undersulfated and 3‐O‐sulfotransferase 3B (3OST‐3B) is overexpressed, as is the case during chronic inflammatory conditions, SARS‐CoV‐2 entry may be facilitated by the glycocalyx. The degree of sulfation and position of the sulfate groups will also affect functions such as immune modulation, the inflammatory response, vascular permeability and tone, coagulation, mediation of sheer stress, and protection against oxidative stress. The rate‐limiting factor to sulfation is the availability of inorganic sulfate. Various genetic and epigenetic factors will affect sulfur metabolism and inorganic sulfate availability, such as various dietary factors, and exposure to drugs, environmental toxins, and biotoxins, which will deplete inorganic sulfate. The role that undersulfation plays in the various comorbid conditions that predispose to coronavirus disease 2019 (COVID‐19), is also considered. The undersulfated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a hyperinflammatory response, vascular permeability, and shedding of the glycocalyx components, giving rise to a procoagulant and antifibrinolytic state and eventual multiple organ failure. These symptoms relate to a diagnosis of systemic septic shock seen in almost all COVID‐19 deaths. The focus of prevention and treatment protocols proposed is the preservation of epithelial and endothelial glycocalyx integrity.
2-MeTHF and CPME were evaluated as greener alternatives for the most employed solvents in peptide synthesis. The ability of these solvents to dissolve amino acid derivatives and a range of coupling reagents were evaluated as well as the swelling of polystyrene and polyethylene glycol resins. In addition, racemization and coupling efficiencies were also determined. We concluded that the use of 2-MeTHF with combination of DIC/OxymaPure gave the lowest racemization level during stepwise synthesis of Z-Phg-Pro-NH2 and the highest purity during SPPS of Aib-enkephalin pentapeptide (H-Tyr-Aib-Aib-Phe-Leu-NH2).
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