Polypeptide-based nanogels possess excellent biocompatibility, stability, and biological functions for many applications. Herein, we present one-pot synthesis of polypeptide nanogels by an innovative strategy of ring-opening polymerization induced nano-gelation of...

Poly­(β-peptoid)­s (N-substituted poly-β-alanines) are an intriguing class of pseudopeptidic materials for biomedical applications, but the polymers prepared by solution polymerization have restricted diversity and functionality due to synthetic difficulty. Synthesis of structurally diverse poly­(β-peptoid)­s is highly desirable yet challenging. Herein, we report a new approach to synthesize skeletal chiral β-peptoid polymers from readily available aspartic acid derivatives. Two types of N-substituted β3-homoalanine monomers, i.e., N-(methyl propionate)-Asp-OMe ( N MeP-Asp-OMe) and N-(tert-butyl propionate)-Asp-OMe ( N tBuP-Asp-OMe), were synthesized in high yield via an aza-Michael addition reaction between l-aspartic acid-1-methyl ester (l-Asp-OMe) and acrylate species. Both N-substituted β3-homoalanines can be readily converted into polymerizable N-substituted β3-homoalanine N-carboxyanhydrides (β-NNCAs). Subsequent ring-opening polymerization (ROP) of these β-NNCA monomers provides access to oligo­(β-peptoid)­s and mPEG-poly­(β-peptoid) diblocks with backbone chirality. Their conformations were preliminarily studied by circular dichroism (CD) spectra and Fourier transform infrared spectroscopy (FT-IR). The synthetic strategy would significantly facilitate the development of novel poly­(β-peptoid)­s with well-defined and diverse structures.