Molecule of the Day: Amoxycillin
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D-Ala-D-ala is a critical component of bacterial cell walls. It is a "crosslink" that acts like a strong net to hold the cells together. Interfering with the machinery that creates these crosslinks creates very weak bacterial cells that soon die. Mammalian cells do not have cell walls or this crosslink, so targeting this part of bacterial biochemistry should be free from side effects in humans!
As can be seen in the extrostatic potential surface diagrams below, penicillins such as amoxycillin have areas of electron density that exactly match those of the D-ala-D-ala crosslink. Therefore, the bacterial enzyme responsible for making the crosslink mistakes penicillins such as amoxycillin for their real target, the D-ala-D-ala. However, penicillins are not just another mimic, they have a chemical surprise in store for any bacterial enzyme that happens to mistake them for D-ala-D-ala (see below).

The very unusual four-membered ring of the penicillins is called a beta-lactam. This ring has a great deal of ring strain in it, so it can be attacked by nucleophiles inside the bacterial enzymes to open the ring as shown below. However, the new bond created with the enzyme is permanent, because reversing the reaction would involve making the strained ring, and this is too unfavorable. The enzyme is covalently linked to the penicillin, and therefore permanently shut down. In other words, the ring strain in the beta-lactam ring is released by reacting with the enzyme, giving such a strong "motive" that the process is essentially irreversible. The bacteria cannot make strong cells walls and they start dying.
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