Single-chain nanoparticles containing sequence-defined segments: using primary structure control to promote secondary and tertiary structures in synthetic protein mimics

Abstract

We investigated intra-chain isocyanide-based multicomponent reactions to synthesize single-chain nanoparticles (SCNP) containing sequence-defined segments at each junction point in order to create materials featuring multiple protein-inspired elements. Upon intramolecular cross-linking, nanoparticle formation ensues, affording materials with well-defined structural elements situated in a disordered tertiary structure. The resulting nanostructures were characterized using ¹H NMR, DOSY NMR, and size-exclusion chromatography. While covalent cross-linking was the intended and predominant mode of SCNP formation, we found that secondary, noncovalent interactions contributed significantly to nanoparticle folding more akin to natural materials.