Synthesis and pH-responsive properties of pseudo-peptides containing hydrophobic amino acid grafts

Abstract

Pseudo-peptidic polymers have been synthesised by grafting L-valine (PV), L-leucine (PL) and L-phenylalanine (PP) onto the pendant carboxylic acid moieties of a pH-responsive polyamide, poly(L-lysine isophthalamide). The pH-responsive aqueous solution properties of PV-75, PL-75 and PP-75 with a stoichiometric degree of substitution of 75 mol% have been compared with those of the parent poly(L-lysine isophthalamide) using UV-visible and fluorescence spectroscopy. At low concentrations (≤0.1 mg mL⁻¹), the grafted polymers displayed pH-dependent conformation. The pH at the onset of hydrophobic association (pH_h) and the pH range over which association occurred varied significantly between the different amino acid grafts. The pH_h values of PV-75, PL-75 and PP-75 at 0.025 mg mL⁻¹ were 6.2, 7.0 and 7.2, respectively. Increasing concentration enhanced intermolecular aggregation. A bis-functional Cy5 derivative, incorporated within the backbones of poly(L-lysine isophthalamide) (polyCy5) and PP-75 (PDP-75), was demonstrated to act as a fluorescence reporter on the state of polymer conformation and aggregation. The intracellular trafficking of PDP-75, examined by confocal microscopy, indicates potential applications of the grafted polymers in drug delivery and medical imaging.