The new science of protein mimetics

New chemistries have been developed for de novo protein design. Protein mimetics of different structural and functional properties such as synthetic peptide ligases and Dn symmetrical helical bundles have been reported. The Template-Assembled Synthetic Protein (TASP) method (as well as the "Molecular Kit" approach) has also been utilized to prepare protein-like molecules. Here we report the synthesis of single chain, scaffold (TRIS)- and dendrimer-assembled collagen mimetics composed of the Gly-Nleu-Pro sequence where Nleu denotes N-isobutyl glycine. From the CD spectra and the thermal denaturation studies it can be seen that the collagen mimetics prepared form stable triple helices except the single chain structure. Furthermore, the 162-residue collagen mimetic dendrimer exhibits enhanced triple helical stability compared to the equivalent scaffold-terminated structure by an increase in the melting temperature in both H2O and 2:1 ethylene glycol/H2O (4 degreesC and 12 degreesC respectively). The concentration dependence for the melting transition of the collagen mimetic dendrimer was measured from which it was determined that the stabilization effect arises from the intramolecular clustering of the triple helical arrays about the core structure. This ensemble excludes solvent from the interior portion of the array which stabilizes the triple helix cluster.