Synthesis and bioevaluation of water-soluble -cyclodextrin-diterpene acid conjugates.

A series of -cyclodextrin (-CD)-conjugates were prepared by combining three abietane-type diterpene acids with two azide-functionalized -CDs via click chemistry, and the antiviral activity against wild-type and omicron SARS-CoV-2 spike pseudovirus as well as the antibacterial activity against were investigated. All the synthesised conjugates exhibited no significant cytotoxicity to BHK-21-hACE2 cells with cell viability over 80% at concentration of 15 M. Among the conjugates, the heptavalent -CD-dehydroabietic acid conjugate exhibited higher anti-SARS-CoV-2 activity against the omicron variant compared to the other conjugates.

Design of Tracers in Fluorescence Polarization Assay for Extensive Application in Small Molecule Drug Discovery.

Development of fluorescence polarization (FP) assays, especially in a competitive manner, is a potent and mature tool for measuring the binding affinities of small molecules. This approach is suitable for high-throughput screening (HTS) for initial ligands and is also applicable for further study of the structure-activity relationships (SARs) of candidate compounds for drug discovery. Buffer and tracer, especially rational design of the tracer, play a vital role in an FP assay system.

Protein Phosphatase 5-Recruiting Chimeras for Accelerating Apoptosis-Signal-Regulated Kinase 1 Dephosphorylation with Antiproliferative Activity.

A normal phosphorylation state is essential for the function of proteins. Biased regulation frequently results in morbidity, especially for the hyperphosphorylation of oncoproteins. The hyperphosphorylation of ASK1 at Thr838 leads to a persistently high activity state, which accelerates the course of gastric cancer.

Beyond Proteolysis-Targeting Chimeric Molecules: Designing Heterobifunctional Molecules Based on Functional Effectors.

In recent years, with the successful development of proteolysis-targeting chimeric molecules (PROTACs), the potential of heterobifunctional molecules to contribute to reenvisioning drug design, especially small-molecule drugs, has been increasingly recognized. Inspired by PROTACs, diverse heterobifunctional molecules have been reported to simultaneously bind two or more molecules and bring them into proximity to interaction, such as ribonuclease-recruiting, autophagy-recruiting, lysosome-recruiting, kinase-recruiting, phosphatase-recruiting, glycosyltransferase-recruiting, and acetyltransferase-recruiting chimeras. On the basis of the heterobifunctional principle, more opportunities for advancing drug design by linking potential effectors to a protein of interest (POI) have emerged.