Design of Cyclic Peptides - Peptide and Protein Design for Biopharmaceutical Applications - page 143

an appropriate protection group strategy for the remaining amino acid
building blocks must be developed. For special cases, like the incorpora-
tion of N-alkylated side chains, standard protocols have been developed
to introduce nonproteinogenic functionalities to amino acids [64].
Further modifications are also feasible as the protection group strategy
was optimized to be orthogonal and compatible to standard Fmoc solid-
phase peptide synthesis (SPPS).
4.2.3.4 Modifications in natural peptides
In nature, e.g. in bacteria, fungi, lower animals and plants, an enor-
mous number of homo- and heterodetic cyclic peptides are found,
including most of the aforementioned alterations [65-67]. Two promi-
nent examples of (poly)cyclic peptides are given in Figure 4.6. On the
left side, vancomycin is shown, which was a last-resort antibiotic until
resistant strains arose in the late 1980s. On the right side, phalloidin
is depicted, which belongs together with the amatoxin family to the
poisonous ingredients of the death cap mushroom ( Amanita
phalloides) . In these examples, typical modifications like (thio)ethers
and adjoined sugars, in combination with nonproteinogenic amino
acids, form cyclic substances that disguise the peptidic origin of the
natural products at first glance.
Figure 4.6 Natural products containing complex cyclic peptide structures. On the
left side is the antibiotic vancomycine and on the right side phalloidin, one of the
poisonous substances composing the death cap mushroom