Beta-lactam
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A beta-lactam ring (β-lactam) is a lactam with a heteroatomic ring structure, consisting of three carbon atoms and one nitrogen atom.[1] A lactam is a cyclic amide.
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[edit] Clinical significance
The beta-lactam ring is part of the structure of several antibiotic families, principally the penicillins, cephalosporins, carbapenems and monobactams, which are therefore also called beta-lactam antibiotics. These antibiotics work by inhibiting the bacterial cell wall synthesis. This has a lethal effect on bacteria, especially on Gram-positive ones. Bacteria can become resistant against beta-lactam antibiotics by expressing beta-lactamase.
[edit] History
The first synthetic β-lactam was prepared by Hermann Staudinger in 1907 by reaction of the Schiff base of aniline and benzaldehyde with diphenylketene[2] [3] in a [2+2]cycloaddition:
[edit] Beta-lactam resistance
Because of the popularity of beta-lactam drugs, certain bacteria have been able to develop counter-measures to traditional drug therapies. An enzyme called beta-lactamase is present in many different types of bacteria, which serves to 'break' the beta lactam ring, which effectively nullifies the antibiotic's effectiveness.
As a response to bacterial resistance to beta-lactam drugs, there are drugs, such as Augmentin/CLA, which are designed to disable the beta-lactamase enzyme. Augmentin/CLA (FGP) is made of amoxicillin, a beta-lactam antibiotic, and clavulanic acid, a beta-lactamase inhibitor. The clavulanic acid is designed to overwhelm all beta-lactamase enzymes, bind irreversibly to them, and effectively serve as an antagonist so that the amoxicillin is not affected by the beta-lactamase enzymes.
[edit] Secondary beta-lactam drug resistance
As a response to decreased efficacy of beta-lactamase, some bacteria have changed the proteins that beta-lactam antibiotics bind, the penicillin binding proteins (PBPs). Since the PBPs no longer recognize the beta-lactams, the antibiotics are essentially useless. This is the mechanism behind the methicillin-resistant Staphylococcus aureus (MRSA).
[edit] Mechanism
Penicillin, a beta-lactam, binds to and inactivates a bacterium's penicillin binding protein (PBP), also known as transpeptidases. PBPs vary in their affinity for binding penicillin or other beta-lactam antibiotics. The amount of PBPs varies between bacterial species. PBPs form transpeptidase bonds in the absence of penicillins or other beta-lactam antimicrobics.
[edit] Side effects
The most common side effect of beta-lactams is fever. Eosinophilia and rash accompany the fever in 25% of patients.
[edit] See also
- ATC code J01C Beta-lactam antibacterials, penicillins
- ATC code J01D Other beta-lactam antibacterials
- Bacteria
[edit] External links
[edit] References
- ^ Gilchrist, T. (1987). Heterocyclic Chemistry. Harlow: Longman Scientific. ISBN 0582014212.
- ^ Tidwell, Thomas T. (2008). "Hugo (Ugo) Schiff, Schiff Bases, and a Century of β-Lactam Synthesis". Angewandte Chemie International Edition 47: 1016. doi:.
- ^ H. Staudinger, Justus Liebigs Ann. Chem. 1907, 356, 51 – 123.
