Concise Modular Synthesis of Thalassotalic Acids A-C.

The novel N-acyldehydrotyrosine analogues known as thalassotalic acids A-C were isolated from a marine bacterium by Deering et al. in 2016. These molecules were shown to have tyrosinase inhibition activity and thus are an attractive set of molecules for further study and optimization. To this end, a concise and modular synthesis has been devised and executed to produce thalassotalic acids A-C and two unnatural analogues. This synthesis has confirmed the identity and inhibitory data of thalassotalic acids A-C, more potent synthetic analogues (IC50 = 65 µM), and provides a route for further structure-activity relationship studies to optimize these molecules.

Targeted degrader technologies as prospective SARS-CoV-2 therapies.

COVID-19 remains a severe public health threat despite the WHO declaring an end to the public health emergency in May 2023. Continual development of SARS-CoV-2 variants with resistance to vaccine-induced or natural immunity necessitates constant vigilance as well as new vaccines and therapeutics. Targeted protein degradation (TPD) remains relatively untapped in antiviral drug discovery and holds the promise of attenuating viral resistance development. From a unique structural design perspective, this review covers antiviral degrader merits and challenges by highlighting key coronavirus protein targets and their co-crystal structures, specifically illustrating how TPD strategies can refine existing SARS-CoV-2 3CL protease inhibitors to potentially produce superior protease-degrading agents.

The Potential of Induced Pluripotent Stem Cells to Treat and Model Alzheimer's Disease.

An estimated 6.2 million Americans aged 65 or older are currently living with Alzheimer's disease (AD), a neurodegenerative disease that disrupts an individual's ability to function independently through the degeneration of key regions in the brain, including but not limited to the hippocampus, the prefrontal cortex, and the motor cortex. The cause of this degeneration is not known, but research has found two proteins that undergo posttranslational modifications: tau, a protein concentrated in the axons of neurons, and amyloid precursor protein (APP), a protein concentrated near the synapse. Through mechanisms that have yet to be elucidated, the accumulation of these two proteins in their abnormal aggregate forms leads to the neurodegeneration that is characteristic of AD. Until the invention of induced pluripotent stem cells (iPSCs) in 2006, the bulk of research was carried out using transgenic animal models that offered little promise in their ability to translate well from benchtop to bedside, creating a bottleneck in the development of therapeutics. However, with iPSC, patient-specific cell cultures can be utilized to create models based on human cells. These human cells have the potential to avoid issues in translatability that have plagued animal models by providing researchers with a model that closely resembles and mimics the neurons found in humans. By using human iPSC technology, researchers can create more accurate models of AD ex vivo while also focusing on regenerative medicine using iPSC in vivo. The following review focuses on the current uses of iPSC and how they have the potential to regenerate damaged neuronal tissue, in the hopes that these technologies can assist in getting through the bottleneck of AD therapeutic research.