The design of covalent inhibitors in glycoscience research is important for the development of chemical biology probes. Here we report the synthesis of a new carbocyclic mechanism-based covalent inhibitor of an α-glucosidase. The enzyme efficiently catalyzes its alkylation via either an allylic cation or a cationic transition state. We show this allylic covalent inhibitor has different catalytic proficiencies for pseudoglycosylation and deglycosylation. Such inhibitors have the potential to be useful chemical biology tools.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.7b05065 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Combatting melioidosis with chemical synthetic lethality.
Proc Natl Acad Sci U S A
November 2024
Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
has emerged as a nonpathogenic surrogate for , the causative agent of melioidosis, and an important Gram-negative model bacterium for studying the biosynthesis and regulation of secondary metabolism. We recently reported that subinhibitory concentrations of trimethoprim induce vast changes in both the primary and secondary metabolome of . In the current work, we show that the folate biosynthetic enzyme FolE2 is permissive under standard growth conditions but essential for in the presence of subinhibitory doses of trimethoprim.
View Article and Find Full Text PDFNovel strategies to overcome chemoresistance in human glioblastoma.
Biochem Pharmacol
December 2024
Beijing Key Laboratory of Environmental and Viral Oncology, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China. Electronic address:
Temozolomide (TMZ) is currently the first-line chemotherapeutic agent for the treatment of glioblastoma multiforme (GBM). However, the inherent heterogeneity of GBM often results in suboptimal outcomes, particularly due to varying degrees of resistance to TMZ. Over the past several decades, O-methylguanine-DNA methyltransferase (MGMT)-mediated DNA repair pathway has been extensively investigated as a target to overcome TMZ resistance.
View Article and Find Full Text PDFMechanism-Based Allylic Carbasugar Chlorides That Form Covalent Intermediates with α- and β-Galactosidases.
Molecules
October 2024
Department of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
Glycoside hydrolases have been implicated in a wide range of human conditions including lysosomal storage diseases. Consequently, many researchers have directed their efforts towards identifying new classes of glycoside hydrolase inhibitors, both synthetic and from natural sources. A large percentage of such inhibitors are reversible competitive inhibitors that bind in the active site often due to them possessing structural features, often a protonatable basic nitrogen atom, that mimic the enzymatic transition state.
View Article and Find Full Text PDFCharge transfer induced phase transition in LiMnOat high pressure.
J Phys Condens Matter
November 2024
High Pressure & Synchrotron Radiation Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Efficient and better energy storage materials are of utmost technological importance to reduce energy dependence on the fossil fuels. LiMnOis one such material having potential to meet most of the requirements for energy storage. This material has been synthesized using solid state synthesis route.
View Article and Find Full Text PDFNoncovalent Inhibition and Covalent Inactivation of Proline Dehydrogenase by Analogs of -Propargylglycine.
Biochemistry
November 2024
Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States.
The flavoenzyme proline dehydrogenase (PRODH) catalyzes the first step of proline catabolism, the oxidation of l-proline to Δ-pyrroline-5-carboxylate. The enzyme is a target for chemical probe discovery because of its role in the metabolism of certain cancer cells. -propargylglycine is the first and best characterized mechanism-based covalent inactivator of PRODH.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!