Design of Cyclic Peptides - Peptide and Protein Design for Biopharmaceutical Applications - page 157

Figure 4.13 Flowchart showing approaches from a chosen protein target to peptidic
and nonpeptidic drugs
4.5 EXAMPLES OF CYCLIC PEPTIDES AS DRUG
CANDIDATES
The following examples will show how small cyclic peptides have
been derived from linear or larger cyclic structures and successfully
implemented into biomedical research. The illustrated peptides are
ligands for transmembrane proteins like integrins or G-protein-coupled
receptors (GPCRs). At present, 40%of all drugs target GPCRs, but so far
only four mammalian GPCRs (rhodopsin, b 1 and b 2 adrenergic receptor
and the human A 2A adenosine receptor) have been structurally deter-
mined [124-127]. In spite of recent successes in homology modelling of
GPCRs, ligand-oriented design or screening is still the usual way to
develop new drugs with GPCRs as target. Therefore, as cyclic peptides
allow a controlled modulation of their spatial structure, they are ideally
suited to explore the unknown conformational space of GPCRs.
4.5.1 Cilengitide as Integrin Inhibitor
Integrins are a class of heterodimeric receptors of one a and one b subunit
found on the surface of most cell lines that facilitate attachment to other