Design of Cyclic Peptides - Peptide and Protein Design for Biopharmaceutical Applications - page 163

hormone somatostatin (t ½ ¼ 1-2 minutes). In vivo , the resulting cyclic
derivative Sandostatin [31] (see Figure 4.17) is much more stable
(t ½ ¼ 70-110 minutes). The enhanced stability is achieved by shifting
the disulfide bridge closer to the active part of the sequence, by introdu-
cing two D -amino acids (the D -Trp 8 in the b-turn, forming the recognition
region, and the N-terminal D -Phe) and by reduction of the C-terminal
carboxyl group of Thr into the corresponding alcohol [169,170].
The cyclic Veber-Hirschmann hexapeptide cyclo(-PFwKTF-) is a
highly active somatostatin agonist [171]. Compared to Sandostatin, it is
an even smaller somatostatin derivative. However, as the hexapeptide is
cyclized from head-to-tail, the two cysteine residues of Sandostatin are
replaced by a dipeptide unit forming a second b-turn. This consists of a
phenylalanine also present in somatostatin and a proline which favours
b-turns when placed in the i þ 1 position, as is the case here.
Figure 4.17 The natural peptide hormone somatostatin (Somatotropin Releasing
Factor, SRIF-14; upper side), the modified octreotide (Sandostatin; right) and the
reduced derivative, called Veber-Hirschmann peptide left [171]. The atoms marked
in dark grey are modified in comparison to somatostatin