Metal-ion catalysed hydrolysis of some β-lactam antibiotics

Gensmantel, Nigel P.; Proctor, Philip; Page, Michael I.

doi:10.1039/p29800001725

Cited by 81 publications

(64 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Transition metal ions produce an enormous increase in the velocity of hydrolysis and aminolysis of penicillins [3,[10][11][12]. It has been proposed that catalysis occurs by means of an intermediate 1:1 complex formed between the metal ion and the antibiotic [10], and that the role of the metal ion in hydrolysis or aminolysis is to establish the tetrahedral intermediate that is formed by the addition of the nucleophilic group to the ␤-lactam carbonyl group [12].…”

Section: Introductionmentioning

confidence: 99%

Penicillin degradation catalysed by Zn(II) ions in methanol

Navarro

Blázquez

Osso

et al. 2003

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Penicillin degradation catalysed by Zn(II) ions in methanol

Navarro

Blázquez

Osso

et al. 2003

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

“…Unlike 277174, the docking results with 193396 showed a hydrogen bonding interaction with the active site residue Asp90, whose carboxylate anion plays a significant role in amide hydrolysis of the lactam ring. 25,29 ( Figure 5). Although the hydrogen bonding with Asp90 occurred between the β-lactam 6-acylamino side chain and the amine hydrogen of Asp90 instead of its carboxyl side chain, 193396 still binds closer to the active site than the other compounds.…”

Section: Resultsmentioning

confidence: 99%

Virtual Screening of Penicillin-derived Inhibitors for the Metallo-β-lactamase from Bacillus cereus

Lee¹,

White²,

Kim³

et al. 2010

Bulletin of the Korean Chemical Society

View full text Add to dashboard Cite

The metallo-β-lactamases (MβLs) are clinically significant enzymes which readily hydrolyze most β-lactam antibiotics. Discovering potential inhibitors for the MβLs is an expensive, time consuming endeavor. Virtual screening can sieve out inhibitor candidates with incompatible features prior to synthesis, decreasing these costs. Using Autodock 4.0, the binding locations and energies of four previously-studied potential inhibitors and four additional compounds obtained from the National Cancer Institute (NCI) database were computationally calculated. Based on the docking models of these eight compounds, we then designed several hypothetical inhibitor structures, compounds A through F, and performed their respective docking experiments. The docking results for compound F showed that it binds to the zinc containing active sites with a lowest predicted binding energy of -6.70 kcal/mol, suggesting F is the most likely potential MβL inhibitor.

show abstract

“…Transition metal ions cause an enormous increase in the rate of hydrolysis of penicillins and cephalosporins [32,33]. For example, Cu(II) ions can enhance the rate of hydrolysis of benzylpenicillin 10 8 -fold -a change in the half-life from 11 weeks to 0.1 s at pH 7.…”

Section: Metal Ion-catalyzed Hydrolysismentioning

confidence: 99%

“…An indication of increased nitrogen basicity would be a large binding constant of penicillin to metal ions. However, the equilibrium constant for metal ion coordination between the carboxyl group and b-lactam nitrogen [6] is only about 100-200 M À1 for Cu(II), Zn(II), Ni(II), and Co(II) [32,33]. This is the order of magnitude expected for coordination between a normal amide and a carboxyl group.…”

Section: Introductionmentioning

confidence: 99%