Helicates, Peptide-Helicates and Metal-Assisted Stabilization of Peptide Microstructures - Metallofoldamers: Supramolecular Architectures from Helicates to Biomimetics - page 290

membrane proteins on the surfaces of cells. RGD binding blocks cell-cell interaction.
This is for example the active mode of the highly toxic protein Echistatin found in the
venom of the viper Echis carinatus [46]. The cell recognition can be used for a novel
concept of cancer therapy. From structure-activity studies it is well known that the RGD
sequence is most active if it is placed in a loop type region of a peptide, as observed in
Echistatin . Thus, many macrocyclic RGD derivatives were prepared, with 27 being the
most prominent [47]. [ 28 MoO 2 ] 2 is easy to obtain by either solution or solid phase
preparation of the ligand followed by complexation of the molybdenum(VI)dioxo unit.
The macrocycle containing the RGD sequence in the ring is obtained quantitatively.

The described examples show that it is possible to prepare simple linear peptide deriva-
tives adopting in their free state a random coil structure. Metal coordination to terminal
binding sites fixes a loop/turn structure, which might possess enhanced bioactivity.

8.4.2 a -Helices
The previous section shows that metal coordination is able to fix peptide units in a specific
structure. a-Helices represent a prominent motif in peptide chemistry which is important
for the interaction of peptides. The a-helix is formed due to intramolecular hydrogen
bonding between amide NH units and carbonyl oxygen atoms. This hydrogen bonding
leads to the helical motif if three amino acid residues separate the hydrogen bond donor
from the corresponding acceptor [48]. A trick for the stabilization of an a-helix is to intro-
duce attractive interactions on one front of the helical column. This can be done by non-
polar amino acids, which are orientated to only one face of the helical “column” and thus
preferably interact with other derivatives (e.g., other a-helices) by hydrophobic interac-
tions. Another approach is to tether two residues which are located in the i and i þ 4 posi-

tions of the peptide strand (Figure 8.19).

Figure 8.19 Two approaches to stabilize a-helical peptide structures.