Tubular Assembly Formation Induced by Leucine Alignment along the Hydrophobic Helix of Amphiphilic Polypeptides.

Mohammed A Abosheasha,Motoki Ueda,Yoshihiro Ito,Toru Itagaki

doi:10.3390/ijms222112075

Abstract

The introduction of α-helical structure with a specific helix–helix interaction into an amphipathic molecule enables the determination of the molecular packing in the assembly and the morphological control of peptide assemblies. We previously reported that the amphiphilic polypeptide SL12 with a polysarcosine (PSar) hydrophilic chain and hydrophobic α-helix (l-Leu-Aib)6 involving the LxxxLxxxL sequence, which induces homo-dimerization due to the concave–convex interaction, formed a nanotube with a uniform 80 nm diameter. In this study, we investigated the importance of the LxxxLxxxL sequence for tube formation by comparing amphiphilic polypeptide SL4A4L4 with hydrophobic α-helix (l-Leu-Aib)2-(l-Ala-Aib)2-(l-Leu-Aib)2 and SL12. SL4A4L4 formed spherical vesicles and micelles. The effect of the LxxxLxxxL sequence elongation on tube formation was demonstrated by studying assemblies of PSar-b-(l-Ala-Aib)-(l-Leu-Aib)6-(l-Ala-Aib) (SA2L12A2) and PSar-b-(l-Leu-Aib)8 (SL16). SA2L12A2 formed nanotubes with a uniform 123 nm diameter, while SL16 assembled into vesicles. These results showed that LxxxLxxxL is a necessary and sufficient sequence for the self-assembly of nanotubes. Furthermore, we fabricated a double-layer nanotube by combining two kinds of nanotubes with 80 and 120 nm diameters—SL12 and SA2L12A2. When SA2L12A2 self-assembled in SL12 nanotube dispersion, SA2L12A2 initially formed a rolled sheet, the sheet then wrapped the SL12 nanotube, and a double-layer nanotube was obtained.

Highlights

In nature, proteins have highly ordered morphologies called tertiary or quaternary structures that are well-defined by precisely controlled packing of secondary structures via various noncovalent interactions such as hydrogen bonding, hydrophobic interactions, van der Waals interactions, electrostatic interactions, π–π interactions, and π–cation interactions [1]
Conticello and coworkers prepared artificial nanotubes with uniform diameters by rational design of the orientation, inclination, and packing of the α-helices using the spatial arrangement of amino acids on the helix [5,6]. His group reported that the helix–helix interaction known as the collagen triple helix is available as a unit for the design of uniformly sized square nanosheets [7,8]. Such a combination of self-assembly of amphiphiles and helix packing controlled by a helix–helix interaction is a promising tool for the fabrication of soft matter with de novo designed morphology and well-defined molecule packing
We previously reported that nanotubes with a uniform diameter of ca. 80 nm were prepared from an amphiphilic block copolypeptide, PSarn-b-(L-Leu-Aib)6 (SL12) with a hydrophobic α-helix composed of the LxLxLxLxLxLx sequence, which involves two LxxxLxxxL sequences [20,21]

Summary

Introduction

Proteins have highly ordered morphologies called tertiary or quaternary structures that are well-defined by precisely controlled packing of secondary structures via various noncovalent interactions such as hydrogen bonding, hydrophobic interactions, van der Waals interactions, electrostatic interactions, π–π interactions, and π–cation interactions [1]. Conticello and coworkers prepared artificial nanotubes with uniform diameters by rational design of the orientation, inclination, and packing of the α-helices using the spatial arrangement of amino acids on the helix [5,6] His group reported that the helix–helix interaction known as the collagen triple helix is available as a unit for the design of uniformly sized square nanosheets [7,8]. Such a combination of self-assembly of amphiphiles and helix packing controlled by a helix–helix interaction is a promising tool for the fabrication of soft matter with de novo designed morphology and well-defined molecule packing

Methods

Results

Conclusion