Structural studies of amphiphilic oligopeptides composed of alternating alanine and ionizable amino-acid residues using CD and 13C CP/MAS NMR spectroscopy

Abstract

We report a novel self-assembling system of amphiphilic oligopeptides composed of alternating hydrophobic and ionizable amino-acid residues. Three types of peptides, AD12, AE12 and AK12, were prepared as building blocks for this model system. These peptides formed helical conformations in low-concentration solutions, but these peptides adopted b-sheet structures and precipitated in highly concentrated solutions at a pH that neutralizes the charges on the ionizable side chains. In addition, the mixing of the peptides with positive and negative charges on the side chains of the ionizable amino-acid residues was found to trigger the formation of the b-sheet structure. This system could be used to create new materials based on oligopeptides. Polymer Journal ( Keywords: alternating arrangement; amphiphilic oligopeptides; 13 C CP/MAS NMR; circular dichroism; self-assembly INTRODUCTIONThe self-assembly of peptides, proteins or their derivatives has been extensively studied and is a promising approach for the design and construction of novel functional nano-materials. Studying this selfassembly also helps clarify the mechanism of diseases. In particular, artificial amphiphilic peptides with exactly alternating hydrophobic and ionizable amino-acid residues have been investigated as candidate building materials based on peptides. This type of amphiphilic peptide is known to self-assemble into b-sheet structures, which then form nanofibers and hydrogels. This self-assembly occurs because one side becomes hydrophobic and the other becomes hydrophilic due to alternating hydrophobic and hydrophilic amino-acid residues in the b-strand. Weak interactions consisting of hydrophobic interactions and charge interactions work together cooperatively to direct the formation of a larger scale architecture. Zhang et al 1 demonstrated that the peptide named EAK16 from the Z-DNA-binding protein Zuotin showed a tendency to self-assemble into a self-supporting gel under physiological pH and salt conditions. 1,2 Since then, many other peptides have been designed to mimic EAK16, and the effects of the sequence and type of hydrophobic residues 3,4 and the effect of a combination of ionizable residues 5,6 on the structural and the physical properties of the self-supporting gels have been studied. These peptide gels have been utilized as biomaterials in constructs such as scaffolds for cell culture in vivo 7-9 and in vitro. 7,9 In addition, gelating peptides responsive to pH, 10 temperature, 11 ionic strength 12 or UV radiation 13 have been developed to improve the handling of peptide-based gels