Effect of Alanine and Glycine on the Assembly of Surfactant‐like Peptides with Tyrosine as Hydrophilic Head in Basic Solution

Surfactant‐like peptides (SLPs) can self‐assemble into various nanostructures, which have shown great potential for a variety of biomedical and biotechnological applications. In this work, two SLPs, V4Y, and V4AGY, were designed and synthesized, both of which had hydrophobic head valines (V) with large side‐chain steric hindrance effect and the hydrophilic head tyrosine (Y) with a rigid ring and two negative charges in the basic solution. Fourier transform infrared and circular dichroism studies confirmed their different secondary structures, whereas atomic force microscopy and dynamic light scattering characterized the difference in their morphologies. In solution, they formed different secondary structures. Correspondingly, V4Y and V4AGY formed noncompact spherical aggregates and a spiral clubbed structure, respectively. In V4AGY, the introduction of alanine (A) and glycine (G) increased the molecule's flexibility and increased the distance between the tyrosine and four continuous valines, so as to weaken the synergistic action of electronic repulsion and steric hindrance and strengthen the intermolecular hydrogen bond beneficial to β‐sheet formation and the axial growth of the self‐assembly. Therefore, the flexibility of the molecule and the side‐chain steric effect of the two heads of SLPs are non‐negligible in the tuning process of peptide self‐assembly, in addition to hydrogen‐bonding, hydrophobic, and electrostatic interactions. Two surfactant‐like peptides, V4Y and V4AGY, formed different secondary structures in a basic solution and formed noncompact spherical aggregates and a spiral clubbed structure, respectively. The effect of the molecular structure on the self‐assembly is discussed from several aspects. The results prove that the flexibility of molecule and the side‐chain steric effect of the two heads of SLPs are non‐negligible in the tuning process of peptide self‐assembly.