Introducing D-amino acid or simple glycoside into small peptides to enable supramolecular hydrogelators to resist proteolysis

Abstract

Here we report the examination of two convenient strategies, the use of a d-amino acid residue or a glycoside segment, for increasing the proteolytic resistance of supramolecular hydrogelators based on small peptides. Our results show that the introduction of d-amino acid or glycoside to the peptides significantly increases the resistance of the hydrogelators against proteinase K, a powerful endopeptidase. The insertion of d-amino acid in the peptide backbone, however, results relatively low storage moduli of the hydrogels, likely due to the disruption of the superstructures of the molecular assembly. In contrast, the introduction of a glycoside to the C-terminal of peptide enhances the biostability of the hydrogelators without the significant decrease of the storage moduli of the hydrogels. This work suggests that the inclusion of a simple glycogen in hydrogelators is a useful approach to increase their biostability, and the gained understanding from the work may ultimately lead to development of hydrogels of functional peptides for biomedical applications that require long-term biostability.

Figure 1

Optical images of the hydrogels of (A) 2 (1.0 wt%, pH 7.0); (B) 3 (1.5 wt%, pH 7.0); (C) 4 (1.5 wt%, pH 7.0); (D) 5 (3.0 wt%, pH 4.0); (E) 6 (3.0 wt%, pH 4.0); and (F) 7 (3.0 wt%, pH 4.0).

Figure 2

Transmission electron micrograph (TEM) of the negative stained hydrogels formed by (A) 2; (B) 3; (C) 4; (D) 5; (E) 6; and (F) 7 shown in Figure 1 (scale bar = 100 nm).

Figure 3

The digestions of hydrogelators (A) 1, 2, 3 and 4; and (B) 5, 6 and 7 over the course of the incubation with proteinase K for 24 hours. All the hydrogelators are at the concentrations of 0.2 wt%.

Figure 4

(A) Strain dependence of the dynamic storage moduli (G’) and the loss moduli (G”) of the hydrogels of 2, 3 and 4 shown in Figure 1; (B) strain dependence of the dynamic storage moduli (G’) and the loss moduli (G”) of the hydrogels of 5, 6 and 7; (C) frequency dependence of the dynamic storage moduli (G’) and the loss moduli (G”) of the hydrogels of 2, 3 and 4 shown in Figure 1; (D) frequency dependence of the dynamic storage moduli (G’) and the loss moduli (G”) of the hydrogels of 5, 6 and 7 shown in Figure 1.

Scheme 1

The molecular structures and the modular representations of the hydrogelators.