Beta-lactam

A beta-lactam ring (β-lactam) is a lactam with a heteroatomic ring structure, consisting of three carbon atoms and one nitrogen atom. A lactam is a cyclic amide.
 * [[Image:Penicillin core.svg|thumb|180px|Penicillin core structure.]]
 * [[Image:Clavulanic acid structure.svg|thumb|180px|[[Clavulanic acid]]]]
 * [[Image:Amoxicillin2.svg|thumb|180px|[[Amoxicillin]]]]
 * [[Image:Ampicillin structure.svg|thumb|180px|[[Ampicillin]]]]
 * [[Image:Flucloxacillin structure.svg|thumb|180px|[[Flucloxacillin]]]]
 * [[Image:Methicillin.png|thumb|180px|[[Methicillin]]]]
 * [[Image:Dicloxacillin.svg|thumb|180px|[[Dicloxacillin]]]]
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 * [[Image:Flucloxacillin structure.svg|thumb|180px|[[Flucloxacillin]]]]
 * [[Image:Methicillin.png|thumb|180px|[[Methicillin]]]]
 * [[Image:Dicloxacillin.svg|thumb|180px|[[Dicloxacillin]]]]
 * }
 * [[Image:Dicloxacillin.svg|thumb|180px|[[Dicloxacillin]]]]
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Clinical significance
The beta-lactam ring is part of the structure of several antibiotic families, the principal ones being the penicillins, cephalosporins, carbapenems, and monobactams, which are, therefore, also called beta-lactam antibiotics. These antibiotics work by inhibiting bacterial cell wall synthesis. This has a lethal effect on bacteria, especially on Gram-positive ones. Bacteria can, however, become resistant against beta-lactam antibiotics by expressing beta-lactamase.

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 in a [2+2]cycloaddition:
 * [[Image:StaudingerLactam.svg]]

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. An example such enzyme is the NDM-1 discovered in 2009.

As a response to bacterial resistance to beta-lactam drugs, there are drugs, such as Augmentin/CLA, that 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.

Secondary beta-lactam drug resistance
As a response to increased efficacy of beta-lactams, some bacteria have changed the proteins that beta-lactam antibiotics bind, the penicillin-binding proteins (PBPs). Since the PBPs are no longer recognized by the beta-lactams, the antibiotics are, in essence, useless. This is the mechanism behind the methicillin-resistant Staphylococcus aureus (MRSA).

Mechanism
Penicillin, a beta-lactam, covalently binds to and inactivates a bacterium's transpeptidase enzyme. Transpeptidase enzymes normally crosslink (i.e., connect) "posts" of 4 stacked amino acids into a "fence," which is the peptide part of peptidoglycan (the rest of the structure is linked sugars that sit on top of the "fence" and further link the "posts"). Peptidoglycan is the outermost and primary component of the cell wall (which protects and coats) in gram-positive bacteria like Streptococcus and Staphylococcus. Transpeptidase or any other protein that binds to penicillin is known as a penicillin-binding protein or PBP. PBPs vary in their affinity for binding penicillin or other beta-lactam antibiotics. The amount of PBPs varies among bacterial species.

Side-effects
The most common side-effects of beta-lactams include allergic reactions and gastrointestinal upset. See individual drug entries for details.

New application
New study has suggested that beta lactam can undergo ring open polymerization to form amide bond, which belongs to nylon-3 polymers. The backbones of these polymers are identical to peptides, which offers them biofunctions. Recent study has showed that these nylon-3 polymers can either work as host defense peptides mimic, or as signal to stimulate 3T3stem cells functions.