文摘
Manipulating the size and shape of noncovalent multivalent assemblies is an ongoing challenge in the field of supramolecular polymers. Following a mechanistic approach, we reasoned that nucleation鈥揺longation kinetics presents unique opportunities for controlled growth since the final outcome is likely to depend on the structure and dynamics of critical-nucleus formation. Taking fibrillar assembly of amyloid 尾 (A尾) peptide as the model system of nucleation-dependent supramolecular polymerization, here we report multivalent polymer鈥損eptide conjugates (mPPCs) that redirect fibrillar assembly of A尾 to form discrete nanostructures. The mPPCs were rationally designed to target A尾 intermediates formed prior to critical nucleation. Atomic force microscopy and transmission electron microscopy studies show that in the presence of mPPCs, A尾 self-assembles into zero-dimensional discrete nanostructures with lateral dimensions approximately in 5鈥?5 nm, while A尾 alone self-assembles into one-dimensional fibrils in micrometer. Thioflavin T kinetics fluorescence assays demonstrate that mPPCs suppress A尾 fibrillogenesis. The mPPCs may thus represent a prototypical molecular design of multivalent macromolecules able to control the final shape of supramolecular polymers assembled via a nucleation-dependent mechanism.