Aqueous Supramolecular Polymers and Peptide Conjugates in Reversible Systems

Supramolecular polymers are of major interest in the field of self assembly with a promising outlook in areas of viscosity modification, compartmentalized architectures, bio-conjugates and drug-delivery applications. They are dynamic macromolecular materials prepared by simple mixing of relatively small components bearing complementary or self-complementary recognition motifs. A major limitation in the field, however, has been access to synthetic systems capable of undergoing self assembly in an aqueous environment. This research proposal develops well-defined, self-organizing macromolecular structures that will overcome this limitation by focusing on systems that rely on several non-covalent interactions occurring in concert rather than on single interactions alone. The envisioned supramolecular polymers and bio-conjugates are designed as dynamic water-soluble smart materials, whose architectures can be controlled and exhibit reversibility upon exposure to external stimuli such as electrochemical, temperature or pH changes. Molecular recognition events occurring between functional handles on both synthetic and bio-polymers will be investigated in order to control the formation of desired functional architectures through stoichiometrically controlled complexation. Preparation of synthetic core motifs to assemble discrete peptide aggregates such as the dimeric through hexameric oligomers of amyloid-beta(40/42) will lead to structural elucidation and insight into several peptide misfolding pathologies like Alzheimer's or Parkinson's disease.