The Design And Synthesis Of Small Molecular Hydrogels Based On Peptoids

Peptide-based molecular hydrogels are formed by the self-assembly of low molecular weight pepttide derivatives via external stimuluses. Several groups have demonstrated their good compatibility by in vitro cell culture experiments and in vivo evaluations. Therefore, they possess big potential for tissue engineering and drug delivery. However, for long term applications in tissue engineering, regenerative medicine, and drug release, the in vivo stability of peptide-based molecular hydrogels needs to be improved. In order to improve their stability, Xu group and Zhang group have developed molecular hydrogelators based on β-peptides, peptides of D-amino acids, nucleic acid-peptide conjugates, and sugar peptides. Compared with peptides of natural amino acids, these gelators of unnatural amino acids showed better stabilities against enzyme digestion or in subcutaneous space in mice model.Unlikeβ-peptides and peptides of D-amino acids, the side chains of peptoids are attached on the nitrogen atom of amide bonds, which prevents the formation of inter-molecular hydrogen bonds between amide bonds. However, peptoids still possessed the ability of self-assembly to form fibers and films via aromatic interactions and charge interactions. We planed to evaluate whether peptoids could also form molecular hydrogels without hydrogen bonds between amide bonds. In this study, we opt to develop molecular hydrogelators consisting of peptoid—pep tide conjugates and evaluate their gelation ability.In summary, we demonstrated that peptoid could be used for the construction of molecular hydrogelators through conjugation to peptides. And the incorporation of peptoids in peptides could greatly enhance the stability of peptide-based molecular hydrogels. The platelet morpology of two of our hydrogels based on peptoid-pepetide conjugates suggested that we might be able to construct two dimensional nanostructures with high density of bioactive peptides, which could enhance the acitivity of peptides via the multivalent interaction. Our observations not only extended the scope of peptide-based molecular hydrogels, but also offer a kind of novel stable molecular hydrogels for controlled drug release and tissue engineering.