2. • 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.
5. Penicillin works by inhibiting an enzyme
involved in the building of bacterial cell walls.
6. 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.
9. Unfortunately penicillins are fragile
C
H
C
H
N C
H
C
C
CH3
CH3
S
NH
O
OH
C
O
R
C
O
What is the bond angle here ?
What does it “want” to be ?
How can it get there ?
10. CH
C
H
NH C
H
C
C
CH3
CH3
S
NH
O
OH
C
O
R C
OH
O
Bacteria that have the enzyme β-lactamase
can hydrolyse the strained amide group.
These are resistant.
Suggest 2 ways of overcoming this resistance.
Why does this resistance spread?
11. 1) Make a
penicillin that
does not fit
into the
active site of
β-lactamase :
Methacillin
2) Inhibit β-
lactamase by
mixing the
active penicillin
with Clavulanic
acid
C
H2
C
H
C N
O
C
C
H
CH
C
O
H
O
CH2 OH
O
C
C
H
C
H
C
N
S
C
C
H
CH3
CH3
C
O
H
O
NH
C
C
CH
C
H
CH C O
O
O
C
C
O
H
H
H
H
H
H