Self-assembled surfactant cyclic peptide nanostructures as stabilizing agents

Abstract

A number of cyclic peptides including [FR]4, [FK]4, [WR]4, [CR]4, [AK]4, and [WK]n (n = 3-5) containing L-amino acids were produced using solid-phase peptide synthesis. We hypothesized that an optimal balance of hydrophobicity and charge could generate self-assembled nanostructures in aqueous solution by intramolecular and/or intermolecular interactions. Among all the designed peptides, [WR]n (n = 3-5) generated self-assembled vesicle-like nanostructures at room temperature as shown by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and/or dynamic light scattering (DLS). This class of peptides represents the first report of surfactant-like cyclic peptides that self-assemble into nanostructures. A plausible mechanistic insight into the self-assembly of [WR]5 was obtained by molecular modeling studies. Modified [WR]5 analogues, such as [WMeR]5, [WR(Me)2]5, [WMeR(Me)2]5, and [WdR]5, exhibited different morphologies to [WR]5 as shown by TEM observations. [WR]5 exhibited a significant stabilizing effect for generated silver nanoparticles and glyceraldehyde-3-phosphate dehydrogenase activity. These studies established a new class of surfactant-like cyclic peptides that self-assembled into nanostructures and could have potential applications for the stabilization of silver nanoparticles and protein biomolecules.

Cyclic peptide-based nanostructures as efficient siRNA carriers

“…arginine and L-glycine were synthesized ( Figure 1) using solid phase peptides synthesis. These peptide sequences (Table 1) were selected based on our previous report where cyclic amphipathic peptides were made consisting of hydrophobic (Trp) and positive charge (Arg) residues [34]. Glycine was incorporated in the sequence to add more flexibility in the peptide.…”

“…Very recently, tryptophan-and arginine-based cyclic peptides were reported to form self-assembled vesiclelike structures and they have been shown to act as molecular transporters. However, self-assembly process of these peptides was time-consuming (10-12 days) and frequency of nanostructures formation was found to be low [34]. Moreover, they were not explored for macromolecular delivery.…”

Self-assembly of peptides to nanostructures

“…44 Recently, we have performed an extensive investigation on the self-assembly process of a number of cyclic peptides including [FR] 4 , [FK] 4 , [WK] 5 , [CR] 4 , [AK] 4 , and [WR] 4 containing L-amino acids (Figure 14). 45 …”

“…The results indicated that three major elements are involved in the self-assembly process of these cyclic peptides including hydrophobic force, hydrogen bonding by partial β-structures, and/or the Π- Π stacking interactions between tryptophan residues. 45 …”

Assessing the interaction between surfactant-like peptides and lipid membranes

“…[1][2][3][4][5] An important class of peptides, which may exhibit a wide range of possibilities for biomedical applications is the amphiphilic peptides. [1][2][3][5][6][7][8][9][10][11][12][13] Despite the various characteristics in common with lipids and detergents, such peptides, called surfactant-like peptides (SLPs), present an intrinsic difference that can lead to different physical consequences: the composition and structure of their tail. Unlike conventional surfactants whose hydrophobic tails interact in all directions through hydrophobic interactions, the amphiphilic peptide tail contains not only hydrophobic groups but also hydrophilic sites.…”