13057-98-2Relevant articles and documents
Tabtoxinine-β-lactam is a "stealth" β-lactam antibiotic that evades β-lactamase-mediated antibiotic resistance
Hart, Kathryn M.,Reck, Margaret,Bowman, Gregory R.,Wencewicz, Timothy A.
, p. 118 - 127 (2016/01/30)
Tabtoxinine-β-lactam (TβL) is a phytotoxin produced by plant pathogenic strains of Pseudomonas syringae. Unlike the majority of β-lactam antibiotics, TβL does not inhibit transpeptidase enzymes but instead is a potent, time-dependent inactivator of glutamine synthetase, an attractive and underexploited antibiotic target. TβL is produced by P. syringae in the form of a threonine dipeptide prodrug, tabtoxin (TβL-Thr), which enters plant and bacterial cells through dipeptide permeases. The role of β-lactamases in the self-protection of P. syringae from tabtoxin has been proposed, since this organism produces at least three β-lactamases. However, using in vitro and cellular assays and computational docking we have shown that TβL and TβL-Thr evade the action of all major classes of β-lactamase enzymes, thus overcoming the primary mechanism of resistance observed for traditional β-lactam antibiotics. TβL is a "stealth" β-lactam antibiotic and dipeptide prodrugs such as tabtoxin from P. syringae represent a novel antibiotic therapeutic strategy for treating multi-drug resistant Gram-negative pathogens expressing high levels of β-lactamase enzymes.
The Micelle-catalysed Hydrolysis of Benzylpenicillin
Gensmantel, Nigel P,Page, Michael I.
, p. 147 - 154 (2007/10/02)
Micelles of cetyltrimethylammonium bromide catalyse the alkaline hydrolysis of benzylpenicillin with a rate enhancement of ca. 50-fold.Howewer, the rate of reaction is inhibited by increasing concentrations of hydroxide ion and penicillin anion.A saturation phenomenon is observed with increased concentration of surfactant.Attempts are made to determine the binding- and rate-constants using existing kinetic models.These are not completely satisfactory and a model is proposed which assumes that both hydroxide ion and penicillin have to be bound to the micelle for reaction to occur.Bromide, chloride, acetate, fluoride, and benzylpenicilloate ions all inhibit the micellar catalysis.
Intra- and Inter-molecular Catalysis in the Aminolysis of Benzylpenicillin
Morris, Jeffrey J.,Page, Michael I.
, p. 212 - 219 (2007/10/02)
The rate law for the aminolysis of benzylpenicillin in water is reported.The Bronsted β-values for the uncatalysed, the amine-catalysed, and hydroxide-ion catalysed reactions are 1.0, 1.09, and 0.96 respectively.This indicates that in the transition states for all three pathways the amine nucleophile contains a unit positive charge which is consistent with the formation of a tetrahedral intermediate.Intramolecular general base catalysis occurs with the reaction of ethylenediamine and, despite the importance of general base catalysis in the aminolysis reaction, the effective concentration of the catalysing base is only ca. 1M, which is attributed to the 'loose' transition state involved in intermolecular catalysis.Intramolecular general acid catalysis occurs with the reaction of ethylenediamine monocation.This suggests that nucleophilic attack takes place from the least hindered α-side.
