Tuning the pH-triggered self-assembly of dendritic peptide amphiphiles using fluorinated side chains

Abstract

We report the synthesis of a series of anionic dendritic peptide amphiphiles of increasing hydrophobic character. By establishing state diagrams we describe their pH and ionic strength triggered self-assembly into supramolecular nanorods in water and highlight the impact of hydrophobic shielding in the supramolecular polymerisation process. Via the incorporation of fluorinated peptide side chains the pH-triggered monomer to polymer transition at physiological ionic strength is shifted from pH 5.0 to pH 7.4. We thereby show that compensating attractive non-covalent interactions and hydrophobic effects with repulsive electrostatic forces, a concept we refer to as frustrated growth, is a sensitive tool in order to manipulate one-dimensional supramolecular polymerisation processes in water.

Mannose‐Decorated Multicomponent Supramolecular Polymers Trigger Effective Uptake into Antigen‐Presenting Cells

“…In aqueous buffer, peptide BM self‐assembles into supramolecular homopolymeric nanorods, with a length of up to 300 nm (Figure ). CD spectroscopic analysis of these supramolecular homopolymers gave rise to a strong negative band at λ =216 nm, which was indicative of β‐sheet‐directed self‐assembly of the hydrophobic oligophenylalanine core …”

Controlling supramolecular polymerization through multicomponent self‐assembly

“…The affinity of the comonomers was increased by incorporating a more hydrophobic leucine amino acid into the peptide chains, which lead to shifts in the apparent p K a values of the amino acid side chains and an increased stability window for the copolymers of pH 2.0–12.0. Similar shifts of the apparent p K a value of up to three units had previously been observed in the supramolecular homopolymerization of amphiphilic dendritic carboxylic acids, which were attributed to be driven by the aggregation process . Note that the group of Hud has developed a similar approach and obtained ultrasensitive and bidirectional pH‐responsive supramolecular polymers and hydrogels .…”

“…Similar shifts of the apparent pK a value of up to three units had previously been observed in the supramolecular homopolymerization of amphiphilic dendritic carboxylic acids, which were attributed to be driven by the aggregation process. [292][293][294] Note that the group of Hud has developed a similar approach and obtained ultrasensitive and bidirectional pH-responsive supramolecular polymers and hydrogels. 295 The system was based on two monomers derived from nucleic acid base pairing mimics using a basic triaminopyrimidine and an acidic cyanuric acid derivative as recognition units.…”

Self-assembling peptide-based building blocks in medical applications

“…Concurrently, the directional forces, such as hydrogen-bonding and π- π stacking, can regulate the larger structure, and lead to formation of core-shell one-dimensional fibril formation. Furthermore, the conformation of the fibril can be tuned by addition of attractive or repulsive electrostatic interaction promoter amino acid [42,43], chemical functionalization [44], or addition of a bulky group [45]. Larger molecules, such as polyethylene glycol (PEG) have also been shown to be useful in therapeutics to enhance their water solubility, reduce immunogenicity, increase in vivo half-life, and aid the self-assembly of peptides and PAs [46–49].…”