A Novel Surfactant with Short Hydrophobic Head and Long Hydrophilic Tail Generates Vesicles with Unique Structural Feature

Surfactant molecules typically have a long hydrophobic tail and a short hydrophilic head group. It remains unexplored if surfactants can have a short hydrophobic head group and a long hydrophilic tail. Designing such surfactants is a challenge as a lengthy hydrophilic tail would completely solubilize the molecules. In this context, herein, the Fmoc-functionalized Gly-Pro-Hyp (GPO) tripeptide repeat-based molecule (Fm-GPO) with fluorenyl moiety as a short hydrophobic head and peptide as a long hydrophilic tail is demonstrated as a reverse surfactant at physiological pH, for the first time. pi-pi stacking of the fluorenyl moieties and intermolecular hydrogen bonding between the peptide chains with extended polyproline-II structure promoted the self-assembly into spherical vesicles with a unique feature of a large hydrophilic area in the interior and exterior of the bilayer. The current Fm-GPO system offers a new class of surfactants with unique features that can aid in the design of drug-loaded vehicles, which can be target-specific as the peptide chain can be manipulated with different functional ultra-short peptide sequences.

Automated summary

In this study, a novel reverse surfactant, Fm-GPO, with a short hydrophobic head group and a long hydrophilic tail, was designed and demonstrated for the first time at physiological pH. Self-assembly of Fm-GPO into spherical vesicles with a large hydrophilic area was promoted by pi-pi stacking of the fluorenyl moieties and intermolecular hydrogen bonding between the peptide chains. This Fm-GPO system provides a new class of surfactants with unique features that can be used for the design of drug-loaded vehicles, which can be target-specific by manipulating the peptide chain with different functional ultra-short peptide sequences.