Page - (000307) - in Biomedical Chemistry: Current Trends and Developments

between scaffold D and an idealized peptide γ-turn, which indicate that this scaffold is a promising γ-turn mimetic. Scaffold D has been experimentally evaluated and has successfully been used to replace two or three amino acids in Ang II, which furnished selective, high affinity pseudopeptides (Table 3.3.2, entries 4 and 5) that act as agonists at the AT2 receptor. Figure 3.3.7: Comparison of Cα distances and angles in an ideal γ-turn model peptide (left) and corresponding atoms in the γ-turn mimicking scaffold D (right). Although the distances and angles correspond well between an idealized γ-turn and scaffold D, such an analysis does not include the incoming and outgoing directions of the peptide backbone or the direction of the side chain of residue i+1. As in the case of the β-turn mimetic classification, one way of characterizing the γ-turn mimetic is to compare relevant parts to a determined 3D structure of a γ-turn. In Fig. 3.3.8, an energy-minimized conformation of scaffold D can be seen superimposed on a γ-turn found in a protein 3D structure, which shows the good match between the structures. Figure 3.3.8: Low energy conformation of scaffold D superimposed on an inverse γ-turn (light grey carbons, PDB ID 1NNF, chain A, sequence Thr82-Ala83-Gln84). For clarity, only Cβ is shown for the side chains and non-polar hydrogen atoms are omitted. 3.3.2 A Case study of Rational Peptide Lead Optimization: Development of Small and Constrained Peptides Targeting the