Solvent Effects on the Self-Assembly of an Amphiphilic Polypeptide Incorporating α-Helical Hydrophobic Blocks

Abstract

The self-assembly of biological molecules is an important pathway to understanding the molecular basis of complex metabolic events. The presence of a cosolvent in an aqueous solution during the self-assembly process can promote the formation of kinetically trapped metastable intermediates. In nature, a category of cosolvents termed osmolytes can work to strengthen the hydrogen-bond network of water such that the native states of certain proteins are favored, thus modulating their function and stability. However, identifying cosolvents that act as osmolytes in biomimetic applications, such as the self-assembly of soft materials, remains challenging. The present work examined the effects of ethanol (EtOH) and acetonitrile (ACN) as cosolvents on the self-assembly of the amphiphilic polypeptide PSar30-(l-Leu-Aib)6 (S30L12), which incorporates α-helical hydrophobic blocks, in aqueous solution. The results provided a direct observation of morphological behavior of S30L12 as a function of solvent composition. Morphological transitions were investigated using transmission electron microscopy, while the packing of peptide molecules was assessed using circular dichroism analyses and evaluations of membrane fluidity. In the EtOH/H2O mixtures, the EtOH strengthened the hydrogen-bond network of the water, thus limiting the hydrophobic hydration of S30L12 assemblies and enhancing hydrophobic interactions between assemblies. In contrast, ACN formed self-associated nanoclusters in water and at the hydrophobic cores of peptide assemblies to stabilize the edges exposed to bulk water and enhance the assembly kinetics. Fourier transform infrared (FT-IR) analysis indicated that both EtOH and ACN can modify the self-assembly of biomaterials in the same manner as osmolyte protectants or denaturants.

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

“…The ethanol injection method initially formed curved sheets of SL12 in milli-Q water. After heat treatment at 90 °C for 1 h, the sheets spontaneously transformed into uniform tubular structures with a diameter of around 80 nm ( Figure 3 A,B,E), which corresponds to previous results [ 21 , 22 , 23 , 25 , 27 , 32 , 33 ]. In contrast, a spherical micelle and vesicle were observed in the dispersion of SL4A4L4, which had the same length of a 12 mer hydrophobic α-helical block as SL12 ( Figure 3 C,D).…”

“…These hydrophilic chain lengths can be treated as the same. The length of 20–30 mers was chosen according to previous work [ 21 , 25 , 27 ]. Next, the secondary structure of the hydrophobic block of the amphiphiles was investigated by CD spectroscopy.…”

“…The amphiphilic polypeptides PSar 28 - b -( l -Leu-Aib) 6 (S28L12) and PSar 27 - b -( l -Leu-Aib) 8 (S27L16) were synthesized as reported previously [ 21 , 22 , 25 , 27 ]. The amphiphilic polypeptides PSar 24 - b -( l -Leu-Aib) 2 -( l -Ala-Aib) 2 -( l -Leu-Aib) 2 (S24L4A4L4) and PSar 26 - b -( l -Ala-Aib)-( l -Leu-Aib) 6 -( l -Ala-Aib) (S26A2L12A2) were synthesized by modifying a reported synthesis scheme [ 21 , 22 , 24 , 27 ] ( Schemes S1 and S2 ). Briefly, dipeptide units of Leu-Aib and Ala-Aib were synthesized with traditional condensation, and the 12 and 16 mer hydrophobic peptide was obtained by combining their units with sequential liquid-phase synthesis.…”

Biphenyl-Induced Superhelix in l -Phenylalanine-Based Supramolecular Self-Assembly with Dynamic Morphology Transitions

“…6,7 The conformational misfolding or disorders in coiled-coil super-helical structures of proteins may disrupt normal cellular metabolism and increase the risk of some diseases including Alzheimer's or Parkinson's diseases. 8,9 Despite the transformation of chiral structures has been modulated in some supramolecular assembled systems via external stimuli such as light, 10,11 pH, 12,13 ions, 14,15 temperature, 16,17 and solvent, 18,19 the involved helical structures are only with simple helix due to rigorous molecular packing mode required for transition from one-dimensional (1D) helical assemblies to higher-order super-helical structures. 20 Therefore, it is a great challenge to fabricate higher level super-helical assemblies and accomplish reversible transformation between initial assemblies and super-helical structures, which is the key to really mimic complex chiral structures related to diverse biological functions.…”

Construction of spatially organized, peptide/peptide derivative containing nanocomposites

“…47,48 The highly designable sequence of peptides renders them versatile building blocks capable of hydrophobic, electrostatic, hydrogen bonding or van der Waals interactions, and these abundantly available interactions motivate peptides to assemble into αhelices, β-sheets, and other higher-order protein complexes. Also, the integrity of resulting peptide-based constructs is maintained by non-covalent interactions, 49,50 which generates Fig. 1 Co-Assembly of amphiphilic building blocks including peptides and peptide derivatives.…”