A series of mercaptophenylacetic acid thiol esters bearing a phenyl substituent adjacent to the carboxylic acid function has been shown to be inhibitors of metallo-beta-lactamases. The inhibition of the Bacteroides fragilis CfiA and Bacillus cereus II metallo-beta-lactamases was Zn2- dependent, greater inhibition being observed at 1 microM ZnSO4 than at 100 microM ZnSO4. Despite this Zn2+ dependency, isothermal titration calorimetry studies illustrated that representative compounds had no detectable affinity for Zn2+ (K > 1 mM). This indicates that their mode of inhibition was not by chelation of the active site Zn2+. Greatest potency was observed against the Stenotrophomonas maltophilia L1 metallo-beta-lactamase with I50 values of between < 1.95 microM and 6 microM and SB-217843 exhibited a similar level of inhibition of this enzyme at 1 and 100 microM Zn2+ (I50 values 5 and 6 microM, respectively). Inhibition of B. cereus II metallo-beta-lactamase by SB-218018 and SB-217782 was competitive with Ki values of 185 microM and 1500 microM, respectively. Therefore, these compounds are specific inhibitors of metallo-beta-lactamases and provide further probes of the active sites of these enzymes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1574-6968.1997.tb12769.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Coupling plasmon and catalytic-active hotspots of Au@Pt core-satellite nanoparticles for in-situ spectroscopic observation of plasmon-promoted decarboxylation.
J Colloid Interface Sci
December 2024
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.
Plasmon-induced hot carriers are a promising "active" energy source, attracting increasing attention for their potential applications in photocatalysis and photodetection. Here, we hybridize plasmonic Au spherical nanoparticles (SNPs) with catalytically active Pt nanocrystals to form Au@Pt core-satellite nanoparticles (CSNPs), which act as both an efficient catalyst for plasmon-promoted decarboxylation reaction and a robust surface-enhanced Raman scattering (SERS) substrate for plasmon-enhanced molecular spectroscopic detection. By regulating the coverage of Pt nanocrystals on the Au SNPs, we modulated the "hotspot" structures of the Au@Pt CSNPs to optimize the SERS detecting capability and catalytic decarboxylation performance.
View Article and Find Full Text PDFDesign of Two New Sulfur Derivatives of Perezone: In Silico Study Simulation Targeting PARP-1 and In Vitro Study Validation Using Cancer Cell Lines.
Int J Mol Sci
January 2024
Departamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán Campo 1, Universidad Nacional Autónoma de México, Avenida 1o de Mayo s/n, Colonia Santa María las Torres, Cuautitlán Izcalli 54740, Mexico.
Poly-ADP-Ribose Polymerase (PARP-1) is an overexpressed enzyme in several carcinomas; consequently, the design of PARP-1 inhibitors has acquired special attention. Hence, in the present study, three compounds (-) were produced through a Michael addition protocol, using phenylmethanethiol, 5-fluoro-2-mercaptobenzyl alcohol, and 4-mercaptophenylacetic acid, respectively, as nucleophiles and perezone as the substrate, expecting them to be convenient candidates that inhibit PARP-1. It is convenient to note that in the first stage of the whole study, the molecular dynamics (MD) simulations and the quantum chemistry studies of four secondary metabolites, i.
View Article and Find Full Text PDFAlkyl Thiocyanurates as Thioester Mimetics. Transthioesterification and Ligation Reactions with High Potential in Dynamic Covalent Chemistry.
J Org Chem
July 2023
Faculty of Chemsitry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Lower Silesia District, Poland.
Alkyl thiocyanurates, the compounds formed in the SN reaction of thiocyanuric acid and alkyl halides, are susceptible to transthioesterification and ligation with molecules containing cysteamine, analogous to native chemical ligation of thioesters with peptides with an N-terminal cysteine moiety. The ligation is irreversible and results in the formation of mono- and disubstituted products dominantly. Transthioesterification, in contrast, is fully reversible and may be used in constructing dynamic systems.
View Article and Find Full Text PDFElectrostatic Assistance of 4-Mercaptophenylacetic Acid-Catalyzed Native Chemical Ligation.
Org Lett
April 2023
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
4-Mercaptophenylacetic acid (MPAA) is a popular catalyst of the native chemical ligation (NCL) but has to be used in large excess for achieving practically useful rates (up to 50-100 equiv). We report here that the catalytic potency of MPAA can be boosted by introducing a stretch of arginines in the departing thiol from the thioester. By doing so, the electrostatically assisted NCL reaction proceeds rapidly by using substoichiometric concentrations of MPAA, an advantage that enables useful synthetic applications.
View Article and Find Full Text PDFThiol Catalysis of Selenosulfide Bond Cleavage by a Triarylphosphine.
J Org Chem
July 2022
Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France.
The arylthiol 4-mercaptophenylacetic acid (MPAA) is a powerful catalyst of selenosulfide bond reduction by the triarylphosphine 3,3',3″-phosphanetriyltris(benzenesulfonic acid) trisodium salt (TPPTS). Both reagents are water-soluble at neutral pH and are particularly adapted for working with unprotected peptidic substrates. Contrary to trialkylphosphines such as tris(2-carboxyethyl)phosphine hydrochloride (TCEP), TPPTS has the advantage of not inducing deselenization reactions.
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!