Page - (000305) - in Biomedical Chemistry: Current Trends and Developments

moiety and the different β-turn types by superimposing important structural features. The main features in a protein turn are the incoming and outgoing directions of the protein backbone and the side chains. If the corresponding directions can be identified in the peptidomimetic moiety, the characterization can be done by superimposing the relevant atoms to the corresponding protein turn structures. The quality of the match can be quantified by the root-mean-square atom pair distance between the two structures. In the case of scaffold C (Fig. 3.3.6) low energy conformations of the scaffold were superimposed to more than 13,000 β-turn structures collected from protein 3D structures in PDB. Out of the well-defined β-turn types, scaffold C had best match to type II β- turns (Fig. 3.3.6) and thus may be suited as a mimetic of this class of β- turns. In angiotensin II (Ang II, Table 3.3.2, entry 1) there have been indications of a turn structure present in the central part of the peptide and scaffold C has been used to replace amino acids in the center of Ang II to yield high affinity Ang II type 1 (AT1) and Ang II type 2 (AT2) receptor ligands (Table 3.3.2, entries 2 and 3). Figure 3.3.6: Low energy conformation of β-turn mimetic scaffold C (dark grey carbons) superimposed to a type II β-turn (light grey carbons; PDB ID 1H2C, chain A, sequence Ile142- Pro143-Asp144-His145). For clarity, only Cβ is shown for the side chains and non-polar hydrogen atoms are omitted. Table 3.3.2: AT1- and AT2 receptor affinity of Ang II and Ang II mimicking pseudopeptides.