Biomedical Engineering Reference
In-Depth Information
FIGURE 8.3
Bicyclic macrocycle obtained by phage display and incorporating a stable
1,3,5-trimethylbenzene bridge.
drug leads when oral bioavailability is needed. Thus, there is a need for technologies
to support diversity generation of less peptidic and nonpeptidic scaffolds, which is
the focus of the next sections.
8.4 PEPTIDOMIMETIC MACROCYCLES
8.4.1 Mimics of Peptide Secondary Structures
Proteases recognize the
-strand conformation in their inhibitors and substrates
[11d,53]. However, most substrate-based protease inhibitors are linear and con-
formationally flexible. Enzyme/inhibitor binding is highly cooperative, whereby
small changes to an inhibitor structure and conformation induce changes to the
