Tunable Chirality of Self-Assembled Dipeptides Mediated by Bipyridine Derivative

Supramolecular peptide assemblies have been widely used for the development of biomedical, catalytical, and optical materials with chiral nanostructures in view of the intrinsic chirality of peptides. However, the assembly pathway and chiral transformation behavior of various peptides remain largely elusive especially for the transient assemblies under out-of-equilibrium conditions. Herein, the N-fluorenylmethoxycarbonyl-protected phenylalanine-tyrosine dipeptide (Fmoc-FY) was used as a peptide assembly platform, which showed that the assembly proceeds multistep evolution. The original spheres caused by liquid-liquid phase separation (LLPS) can nucleate and elongate into the formation of right-handed helices which were metastable and easily converted into microribbons. Interestingly, a bipyridine derivative can be introduced to effectively control the assembly pathway and induce the formation of thermodynamically stable right-handed or left-handed helices at different stoichiometric ratios. In addition, the chiral assembly can also be regulated by ultrasound or enzyme catalysis. This minimalistic system not only broadens the nucleation-elongation mechanisms of protein aggregates but also promotes the controllable design and development of chiral biomaterials. The self-assembly of an N-terminal-protected phenylalanine-tyrosine dipeptide has been shown to proceed by multistep structural evolution involving spheres, right-handed helices and microribbons .A bipyridine derivative was introduced at different stoichiometric ratios to obtain thermodynamically stable chiral nanostructures (right- or left-handed helices). Ultrasound and enzyme catalysis are also effective strategies to regulate the chirality.image