Molecular design of functional peptides by utilizing unnatural amino acids: Toward artificial and photofunctional protein

AbstractUnnatural amino acids are effective as building blocks to design functional peptides from the following two points: (1) utilization of rigid unnatural amino acids for the incorporated peptides to control the conformation to appear the function, and (2) incorporation of functional and unnatural amino acids into peptides resulting in appearance of the inherent functions. As a combined strategy, molecular design of artificial metalloproteins utilizing 5′‐amino‐2,2′‐bipyridine‐5‐carboxilic acid (H–5Bpy–OH) as an unnatural amino acid is proposed. The peptide containing three residues of the unnatural amino acid would fold through coordination to a metal ion. In particular, ruthenium(II) ion would yield a ruthenium tris(bipyridine) derivative as the core complex of the artificial protein, which would appear the similar photochemical functions as that of ruthenium(II) tris(bipyridine) complex. The central complex could form two isomers, fac and mer. For selective synthesis of the mer complex, which is expected as the core complex in the artificial protein, dicyclohexylamide as a bulky group is introduced at the C‐terminal of the unnatural amino acid to destabilize the fac complex due to steric hindrance. Furthermore, in order to know the photochemical properties and function of the protein mimics, ruthenium(II) tris(2,2′‐bipyridine) complexes bearing amide groups at 5,5′ positions have been synthesized as the model complexes. As a result, the direction of amide groups (RNHCOor RCONH) in ruthenium complexes is found to significantly affect the emission efficiency: the former reduces the quantum yield and the latter enhances it, respectively. The ruthenium(II) tris(5,5′‐diamide‐2,2′‐bipyridine) complexes are also found to strongly bind with various anions [e.g., halogen ions (Cl−, Br−) and acetate anion] in acetonitrile and to detect these anions through the emission spectral changes under air. The molecular design of artificial protein is expected to develop new fields among peptide, organic, inorganic, and physical chemistry. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004