ArticleBiochemical pharmacology2012
Inactivation of a class A and a class C β-lactamase by 6β-(hydroxymethyl)penicillanic acid sulfone.
Article in Biochemical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 19 citations in OpenAlex.
- Application of Nanoparticle Technology to Reduce the Anti-Microbial Resistance through β-Lactam Antibiotic-Polymer Inclusion Nano-Complex.Pharmaceuticals (Basel, Switzerland) · 2018Article
- Exploring Additional Dimensions of Complexity in Inhibitor Design for Serine β-Lactamases: Mechanistic and Intra- and Inter-molecular Chemistry Approaches.Frontiers in microbiology · 2018Review
- Search for non-lactam inhibitors of mtb β-lactamase led to its open shape in apo state: new concept for antibiotic design.Scientific reports · 2017Article
- One ring to rule them all: Current trends in combating bacterial resistance to the β-lactams.Protein science : a publication of the Protein Society · 2016Review
- Detecting a quasi-stable imine species on the reaction pathway of SHV-1 β-lactamase and 6β-(hydroxymethyl)penicillanic acid sulfone.Biochemistry · 2015Article
- A kinetic analysis of the inhibition of FOX-4 β-lactamase, a plasmid-mediated AmpC cephalosporinase, by monocyclic β-lactams and carbapenems.The Journal of antimicrobial chemotherapy · 2014Article
- Penam sulfones and β-lactamase inhibition: SA2-13 and the importance of the C2 side chain length and composition.PloS one · 2014Article
- New β-lactamase inhibitors: a therapeutic renaissance in an MDR world.Antimicrobial agents and chemotherapy · 2014Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
β-Lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) contribute significantly to the longevity of the β-lactam antibiotics used to treat serious infections. In the quest to design more potent compounds and to understand the mechanism of action of known inhibitors, 6β-(hydroxymethyl)penicillanic acid sulfone (6β-HM-sulfone) was tested against isolates expressing the class A TEM-1 β-lactamase and a clinically important variant of the AmpC cephalosporinase of Pseudomonas aeruginosa, PDC-3. The addition of the 6β-HM-sulfone inhibitor to ampicillin was highly effective. 6β-HM-sulfone inhibited TEM-1 with an IC(50) of 12 ± 2 nM and PDC-3 with an IC(50) of 180 ± 36 nM, and displayed lower partition ratios than commercial inhibitors, with partition ratios (k(cat)/k(inact)) equal to 174 for TEM-1 and 4 for PDC-3. Measured for 20 h, 6β-HM-sulfone demonstrated rapid, first-order inactivation kinetics with the extent of inactivation being related to the concentration of inhibitor for both TEM-1 and PDC-3. Using mass spectrometry to gain insight into the intermediates of inactivation of this inhibitor, 6β-HM-sulfone was found to form a major adduct of +247 ± 5 Da with TEM-1 and +245 ± 5 Da with PDC-3, suggesting that the covalently bound, hydrolytically stabilized acyl-enzyme has lost a molecule of water (HOH). Minor adducts of +88 ± 5 Da with TEM-1 and +85 ± 5 Da with PDC-3 revealed that fragmentation of the covalent adduct can result but appeared to occur slowly with both enzymes. 6β-HM-sulfone is an effective and versatile β-lactamase inhibitor of representative class A and C enzymes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.