Advances in the development of Wnt/β-catenin signaling inhibitors.

The Wnt/β-catenin signaling pathway plays a critical role in various biological processes, including cell proliferation, differentiation, and tissue homeostasis. Aberrant activation of this pathway is strongly associated with the development of various cancers, including colorectal, pancreatic, and gastric cancers, making it a promising therapeutic target. In recent years, inhibitors targeting different components of the Wnt/β-catenin pathway, including small molecules, peptides, and nucleic acid-based therapies, have been developed to suppress cancer cell growth.

Magainin 2-derived stapled peptides derived with the ability to deliver pDNA, mRNA, and siRNA into cells.

We have developed cell-penetrating stapled peptides based on the amphipathic antimicrobial peptide magainin 2 for intracellular delivery of nucleic acids such as pDNA, mRNA, and siRNA. Various types of stapled peptides with a cross-linked structure were synthesised in the hydrophobic region of the amphipathic structure, and their efficacy in intracellular delivery of pDNA was evaluated. The results showed that the stapled peptide st7-5 could deliver pDNA into cells.

Structure-activity relationship study of PROTACs against hematopoietic prostaglandin D synthase.

Degradation of hematopoietic prostaglandin D synthase (H-PGDS) by proteolysis-targeting chimeras (PROTACs) is expected to be important in the treatment of allergic diseases and Duchenne's muscular dystrophy. We recently reported that 7 (1), which is composed of H-PGDS inhibitor (TFC-007) and cereblon (CRBN) E3 ligase ligand (pomalidomide), showed potent H-PGDS degradation activity. Here, we investigated the structure-activity relationships of 1, focusing on the C4- or C5-conjugation of pomalidomide, in addition, the H-PGDS ligand exchanging from TFC-007 with the biaryl ether to TAS-205 with the pyrrole.

Characterization of stereospecific enoyl reductase ActVI-ORF2 for pyran ring formation in the actinorhodin biosynthesis of Streptomyces coelicolor A3(2).

Actinorhodin (ACT) is a benzoisochromanequinone antibiotic produced by Streptomyces coelicolor A3(2), which has served as a favored model organism for comprehensive studies of antibiotic biosynthesis and its regulation. (S)-DNPA undergoes various modifications as an intermediate in the ACT biosynthetic pathway, including enoyl reduction to DDHK. It has been suggested that actVI-ORF2 encodes an enoyl reductase (ER).

Molecular recognition of SARS-CoV-2 spike glycoprotein: quantum chemical hot spot and epitope analyses.

Due to the COVID-19 pandemic, researchers have attempted to identify complex structures of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S-protein) with angiotensin-converting enzyme 2 (ACE2) or a blocking antibody. However, the molecular recognition mechanism-critical information for drug and antibody design-has not been fully clarified at the amino acid residue level. Elucidating such a microscopic mechanism in detail requires a more accurate molecular interpretation that includes quantum mechanics to quantitatively evaluate hydrogen bonds, XH/π interactions (X = N, O, and C), and salt bridges.

Single reference quantitative analysis of xanthomonasin A and B in Monascus yellow colorant using high-performance liquid chromatography with relative molar sensitivity based on high-speed countercurrent chromatography.

Monascus yellow (MY) is a natural yellow food coloring. The main components from MY are xanthomonasin A (XA) and xanthomonasin B (XB) for natural yellow colorant of food additives. However, few chromatographic assays of XA and XB exist in food additive products because of unavailable standards for calibration curves.