Biomedical Engineering Reference
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and a
D
-amino acid or alanine scan to determine the importance of
chirality and of the side chain of each constituent amino acid. This
allows the identification of the groups that are important for bind-
ing to the receptor and for signal transduction. In order to optimize
the steric and electronic properties of the peptide, and to limit its
metabolic breakdown, extensive use is made of modified or non-
coded a-amino acids. Successful examples of extensively modified
peptides include the GnRH antagonist Ganirelix and the Bradykinin
B
2
antagonist Icatibant (Figure 3.2).
pGlu - His - Trp - Ser - Tyr - Gly - Leu - Arg - Pro - Gly - NH
2
GnRH
Ac - D-2Nal - D-4Cpa - D-3Pal - Ser - Tyr - D-Har(Et)
2
- Leu - Har(Et)
2
- Pro - D-Ala - NH
2
Ganirelix
HN
HN
HN
N
HN
N
N
OH
O
O
O
O
O
H
N
H
N
H
N
H
N
O
N
H
H
H
H
H
NH
2
O
O
O
O
O
O
Cl
OH
Bradykinin
H - Arg - Pro - Pro - Gly - Phe - Ser - Pro - Phe - Arg - OH
H - D-Arg - Arg - Pro - Hyp - Thi - Ser - D-Tic - Oic - Arg - OH
Icatibant (HOE 140)
NH
2
HN
HN
NH
2
NH
OH
NH
H
S
H
O
N
O
N
O
O
N
OH
N
N
H
2
N
O
N
H
H
N
O
O
O
O
OH
NH
HN
NH
2
Figure 3.2 Structure of modified GnRH and Bradykinin analogues
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