Penicillin

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Penicillin
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• 1928 Alexander Fleming noticed that a mould
  (penicillium notatum) produced a compound that
  inhibits bacterial growth.
• 1940 Florey and Chain showed that an injection
  of extract cured infections in mice and later in
  humans.
• 1945 Fleming, Florey and Chain were awarded a
  Nobel Prize for Medicine.

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Penicillin-G
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Penicillin works by inhibiting an enzyme involved
in the building of bacterial cell walls.
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The mould extract was broken down if taken by
mouth and effective only against a limited range
of bacteria.
In the 1950s it was shown that penicillin-G could
be broken down to give 6-amino penicinillic acid
from which a range of semi- synthetic penicillins
could be made.
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6-APA
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Unfortunately penicillins are fragile
What is the bond angle here ?
What does it want to be ?
How can it get there ?
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Bacteria that have the enzyme ß-lactamase can
hydrolyse the strained amide group. These are
resistant.
Why does this resistance spread?
Suggest 2 ways of overcoming this resistance.
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• Make a penicillin that does not fit into the
  active site of ß-lactamase Methacillin

2) Inhibit ß-lactamase by mixing the active
penicillin with Clavulanic acid