Design of Cyclic Peptides - Peptide and Protein Design for Biopharmaceutical Applications - page 162

Figure 4.16 Left: derivatization of polyphemusin II into a cyclic pentapeptide with
excellent antagonistic activity on CXCR4. Optimization of the residues marked in red
led from the initial peptide to its shortened analogue (middle). The amino acids
marked in blue and an additional glycine were subjected to the spatial screening.
Right: cartoon of the backbone structure with disulfide bonds of the polyphemusin II
analogue tachyplesin I, showing the regions of interest in colours corresponding to the
scheme on the left (see colour Plate 4)
tetrapeptidic scaffolds. However, the most promising has been N-methy-
lation of the arginine ( D -configured, in contrast to the starting compound)
next to the D -tyrosine, with further enhancement of affinity [168].
4.5.3 Sandostatin and the Veber-Hirschmann Peptide as
Examples of Rational Design
Somatostatins are a family of cyclopeptides that exhibit a broad inhibi-
tory effect on the secretion of hormones like insulin, glucagon and growth
hormones. Therefore, their derivatives are used in the treatment of acro-
megaly and endocrine tumours [169].
A remarkable example of the (semi)rational design of a drug candidate
is the chemical modification of the metabolically unstable peptide