Total syntheses of two recently discovered proteasome inhibitors, syringolin A and B, are reported. The key to our approach was creation of the alpha,beta-unsaturated 12-membered lactam via intramolecular Horner-Wadsworth-Emmons reaction. Such reactions have been broadly used to prepared macrolactones, but this work presents a rarer example of its application to macrolactams. The final steps involved attachment of the bis(valinyl)urea side chain using peptide coupling procedures, including a method based on the unprotected valine N-carboxy anhydride. The additional alkene of syringolin A was created through cross-metathesis.

Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer’s disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-β (Aβ) peptides at residues 12-28 of Aβ and this binding modulates Aβ accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aβ interaction with Aβ12-28 P reduced Aβ and tau-related pathology, leading to cognitive improvements in treated AD mice. Recently, we have designed a small peptoid library derived from the Aβ12-28 P sequence to screen for new apoE/Aβ binding inhibitors with higher efficacy and safety. Peptoids are better drug candidates than peptides due to their inherently more favorable pharmacokinetic properties. One of the lead peptoid compounds, CPO_Aβ17–21 P, diminished the apoE/Aβ interaction and attenuated the apoE4 pro-fibrillogenic effects on Aβ aggregation in vitro as well as apoE4 potentiation of Aβ cytotoxicity. CPO_Aβ17–21 P reduced Aβ-related pathology coupled with cognitive improvements in an AD APP/PS1 transgenic mouse model. Our study suggests the non-toxic, non-fibrillogenic peptoid CPO_Aβ17–21 P has significant promise as a new AD therapeutic agent which targets the Aβ related apoE pathway, with improved efficacy and pharmacokinetic properties.

Since the identification of the first human coronavirus in the 1960s, a total of six coronaviruses that are known to affect humans have been identified: 229E, OC43, severe acute respiratory syndrome coronavirus (SARS-CoV), NL63, HKU1, and Middle East respiratory syndrome coronavirus (MERS-CoV). Presently, the human world is affected by a novel version of the coronavirus family known as SARS-CoV-2, which has an extremely high contagion rate. Although the infection fatality rate (IFR) of this rapidly spreading virus is not high (ranging from 0.00% to 1.54% across 51 different locations), the increasing number of infections and deaths has created a worldwide pandemic situation. To provide therapy to severely infected patients, instant therapeutic support is urgently needed and the repurposing of already approved drugs is presently in progress. In this regard, the development of nanoparticles as effective transporters for therapeutic drugs or as alternative medicines is highly encouraged and currently needed. The size range of the viruses is within 60-140 nm, which is slightly larger than the diameters of nanoparticles, making nanomaterials efficacious tools with antiviral properties. Silver-based nanomaterials (AgNMs) demonstrate antimicrobial and disinfectant effects mostly by generating reactive oxygen species (ROS) and are presently considered as a versatile tool for the treatment of COVID-19 patients. Other metal-based nanoparticles have been primarily reported as delivery agents or surface modifying agents, vaccine adjuvant against coronavirus. The present review summarizes and discusses the possible effectiveness of various surface-modified AgNMs against animal coronaviruses and presents a concept for AgNM-based therapeutic treatment of SARS-CoV-2 in the near future.

Adsorption of organic pollutants, toxic metal ions, and removal of harmful bacteria can give us clean and pure drinkable water from wastewater resources. Respective magnetite nanoparticles (MNPs) were synthesized using a cheaper and greener way in an open-air environment with the use of crude latex of Jatropha curcas (JC) and leaf extract of Cinnamomum tamala (CT). Characterization of MNPs had been performed by dynamic light scattering (DLS), Ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, powdered X-ray diffraction (XRD), and field emission scanning electron microscope (FE-SEM). The size ranges of the synthesized MNPs were observed in between 20–42 nm for JC-Fe3O4 and within 26–35 nm for CT-Fe3O4 by FE-SEM images. The effect of synthesized magnetic nanoparticles in wastewater treatment (bacterial portion), dye adsorption, toxic metal removal as well as antibacterial, antioxidant, and cytotoxic activities were studied. This purification will lead to an increase in the resources of pure drinking water in the future.

The terminal amino groups of peptoids have often been protected with acetyl groups to improve cell permeability and therapeutic potential, and to prevent the poisoning of the catalysts in organometallic reactions. Interestingly, the unusual truncation of the terminal peptoid unit has sometimes been encountered when the acetylated linear peptoids were treated with a TFA cleavage cocktail. In this study, we systematically investigated the electronic effects of acyl groups on the truncation of N-acylated peptoids to rationalize the formation of the deleted peptoids and to establish an appropriate strategy for preventing such undesired truncation.