Hierarchical Self‐assembly of G‐Quadruplexes Based Hydrogel Consisting of Guanine and Peptide Epitope†

Abstract

Comprehensive SummaryGuanosine‐based hydrogels have attracted considerable attention because of their simplicity and easy preparation. However, the sugar moiety limits its further applications because of the necessity of sugar in the hydrogel formation. This work reports a G‐quadruplexes‐based hydrogel consisting of guanine and peptide epitope to form a supramolecular hydrogel in the presence of metal cations. Using the metal ion‐responsive peptide epitope from the ion channel to replace sugar motif at N9 position of guanosine results in a novel nucleopeptide. The results show that the gelation time, the diameter of nanofibers, the anisotropic property, and the mechanical property of the hydrogel can be simply controlled using metal cations. The magnesium and calcium ions direct the alignment of nanofibers to form anisotropic nano‐bundles. The mechanistic studies indicate the formation of G‐quadruplexes in the hydrogel. Compared to the storage modulus of nucleopeptide without the metal cation, adding zinc ions results in an over three‐order increase in mechanical properties. Cytotoxicity experiment indicates the good biocompatibility of our hydrogel. Moreover, we demonstrate that the guanine‐capped peptide could release STING agonist in a controlled manner. This work illustrates a simple way to modulate the property of the nucleopeptide hydrogel to develop soft materials.