Chemistry Reference
In-Depth Information
HO
NH
2
*
Me
O
Me
OH
OH
*
*
*
*
O
*
*
*
CH
2
OH
*
O
O
Cl
D-
O
-E
C-
O
-D
O
O
Cl
HO
OH
O
O
*
*
H
N
H
N
H
N
*
*
*
*
N
H
NH
O
*
H
H
H
H
O
O
NHMe
H
AB
O
O
*
H
NH
2
*
HO
2
C
OH
OH
HO
7
Dpg
5
Hpg
4
Hpg
6
Cht
3
Asn
2
Cht
1
Leu
Scheme 2-3. Stereochemical features of the vancomycin structure. The AB-ring (chiral axis)
and
the
C-O-D-O-E-rings
(chiral
planes)
fixate
the
heptapeptide
aglycon
in
a
rigid
comformation.
The side-chain cyclizations are the basis for conformative rigidity of the molecules
and thus for the antibiotic activity of glycopeptide antibiotics.
2.3
MODE OF ACTION
Various antibacterial targets exist, in which antibiotics interfere with the essential
pathways of the bacterial metabolism. These targets are the interaction with the cyto-
plasmic membrane, the inhibition of cell wall biosynthesis, or the inhibition of repli-
cational, transcriptional, and translational processes. Like the penicillins and the
cephalosporins, glycopeptide antibiotics also inhibit the cell wall biosynthesis.
According to the features of the bacterial cell wall, bacteria are divided into gram-
positive and gram-negative organisms. Gram-negative bacteria (e.g., Escherichia
coli) have a thin layer of peptidoglycan that is covered by an outer membrane.
Gram-positive bacteria (e.g., S. aureus) lack this outer membrane but have a thicker
peptidoglycan layer compared with gram-negative organisms. Because of their size
and polarity, glycopeptide antibiotics cannot cross the outer membrane of gram-
negative bacteria, and thus, their antibiotic effects are restricted to gram-positive bac-
teria. As a consequence, the most important bacterial strains, which are combated
with glycopeptides, are gram-positive enterococci, staphylococci, and streptococci.
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