Glycoside hydrolases are important enzymes in a number of essential biological processes. Irreversible inhibitors of this class of enzyme have attracted interest as probes of both structure and function. In this review we discuss some of the compounds used to covalently modify glycosidases, their use in residue identification, structural and mechanistic investigations, and finally their applications, both in vitro and in vivo, to complex biological systems.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1093/glycob/cwn041 | DOI Listing |
J Med Chem
January 2025
Chief executive officer, Jacobio Pharmaceuticals Group Co., Ltd., Beijing100176, P. R. China.
KRAS is the most frequently mutated driver oncogene in human cancer, and KRAS mutation is commonly found in non-small-cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). Inhibitors that covalently modify the mutated codon 12 cysteine have completed proof-of-concept studies in the clinic. Here, we describe structure-based design and cocrystal-aided drug optimization of a series of compounds with the 1,8-naphthyridine-3-carbonitrile scaffold.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
In the last few years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the cause of a worldwide pandemic, highlighting the need for novel antiviral agents. The main protease (M) of SARS-CoV-2 was immediately identified as a crucial enzyme for viral replication and has been validated as a drug target. Here, we present the design and synthesis of peptidomimetic M covalent inhibitors characterized by quinoline-based P moieties.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China, 310014. Electronic address:
Ethnopharmacological Relevance: The Chinese medicine sappanwood is primarily sourced from the dried heartwood of the medicinal plant Caesalpinia sappan Linn., which has been found with a variety of valuable properties including anti-inflammatory, anti-oxidant, and anti-viral effects. Preliminary investigations have demonstrated that sappanwood showed strong anti-SARS-CoV-2 M effects, but the key constituents responsible for SARS-CoV-2 M inhibition and their anti-M mechanisms have not been uncovered.
View Article and Find Full Text PDFJ Med Chem
January 2025
Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS.
View Article and Find Full Text PDFProtease-activated receptor 2 (PAR2) is a central regulator of intestinal barrier function, inflammation and pain. Upregulated intestinal proteolysis and PAR2-signaling are implicated in inflammatory bowel diseases (IBDs) and irritable bowel syndrome (IBS). To identify potential bacterial regulators of PAR2 activity, we developed a functional assay for PAR2 processing and used it to screen conditioned media from a library of diverse gut commensal microbes.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!