Biomedical Engineering Reference
In-Depth Information
A wide range of such modified amino acids are now commercially
available, which facilitates the application of this strategy to optimize
the pharmacological profile of bioactive peptides.
The consideration that the interaction of a peptide with its biological
receptor would mainly involve the side chains led to the interesting concept
that a reversal of the peptide bond from CO-NH to NH-CO in a peptide
would increase the metabolic stability, while maintaining the receptor affinity
[7]. The topographical similarity of a peptide structure with its retroenantio-
meric structure was first recognized for cyclic peptides [4] (Figure 3.3). In the
cycloretroenantiomer, the sequence of the peptide was reversed, and the
configuration of each residue was inverted. Although differences in side-
chain topology were noted [8], the concept of cycloretroenantiomerization
has been applied successfully to many peptide sequences [9]. In a recent
application, a library of retroenantiomeric cyclic pentapeptides was used to
develop a CXCR4 antagonist that is more potent than the parent peptide [10]
(Figure 3.3). Also, the cyclic osteogenic growth peptide C-terminal peptide
OGP(10-14) and its retroenantiomer were shown to be equipotent [11].
R
1
O
R
1
NH
R
2
O
cycloretro-
enantiomers
R
2
NH
HN
HN
O
O
O
O
NH
HN
R
4
NH
O
R
4
HN
R
3
O
R
3
OH
OH
O
N
O
NH
N
H
HN
cycloretro-
e
nantiomers
O
O
O
NH
O
O
HN
O
NH
HN
NH
O
NH
NH
2
NH
NH
2
H
2
N
H
2
N
H
O
N
H
HN
NH
HN
NH
CXCR4 antagonist
OH
O
O
H
N
OH
O
HN
NH
NH
O
HN
O
O
HN
O
NH
NH
HN
H
O
O
O
cyclic OGP(10-14)
cyclic retroinverso OGP(10-14)
Figure 3.3 Cyclic peptides and their cycloretroenantiomers
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