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

Abstract

Unnatural 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.

Synthesis and evaluation of benzothiazolyl and benzimidazolyl asparagines as amino acid based selective fluorimetric chemosensors for Cu2+

“…7e10 Unnatural amino acids with intrinsic functions have been increasingly studied, to be incorporated into peptides. 18,19 A strategy for the development of such compounds involves the incorporation of multidentate complexing ligands in amino acid residues in the form of heterocyclic moieties. Amino acids bearing 2,2 0 -bipyridine and 1,10-phenanthroline have been used in the synthesis of metallopeptides that bind Zn 2þ .…”

Synthesis and photophysical characterization of new fluorescent bis-amino acids bearing a heterocyclic bridge containing benzoxazole and thiophene

“…4 The molecular design of functional peptides can thus be achieved by judicious choice of unnatural amino acids of natural and synthetic origin which are effective building blocks for peptide design considering the following two points: i) use of rigid unnatural amino acids to control the conformation and function of the resulting peptides and ii) incorporation of functional unnatural amino acids into peptides resulting in the appearance of the inherent functions. 5 Benzoxazoles display excellent optical properties (broad spectral windows, high molar absorptivity coefficients and fluorescence quantum yields) and they have been described as fluorescent probes and sensing materials, namely as fluorescent and/or colorimetric sensors for metals, anionic species and in pharmaceutical analysis. 6 Thiophene and its derivatives also possess important electroluminescent properties with wide application in polymer science, which has prompted their application as energy transfer and light-harvesting systems, for optical and electronic devices, 7 as sensors and as fluorescent markers.…”

“De Novo” Design of Peptides with Specific Lipid-Binding Properties

“…Modified or non-natural amino acids are notably used to study the folding, the conformational stability, and the flexibility of peptides and proteins (5)(6)(7)(8)(9). Non-natural amino acids can be more resistant to protease degradation and have a decreased immunogenicity (10).…”