We are interested in chemical tool development using synthetic organic chemistry for molecular recognition driven applications in biology.
1) Peptidomimetic Strategy for Amyloid Inhibition: Uncontrolled fibrillation of the amyloid-beta (Aβ) peptide results in the formation of β-sheet-rich amyloid plaques in the central nervous system of Alzheimer’s Disease patients. A supramolecular strategy based on the assembly of peptidomimetic agents into functional vesicles has been conceived for the inhibition of Aβ fibrillation. Tris-pyrrolamide peptidomimetic readily forms vesicles under physiological conditions. These vesicles completely rescue both mouse neuroblastoma N2a and human neuroblastoma SH-SY5Y cells from the cytotoxicity that follows from Aβ misfolding. (J. Am. Chem. Soc., 2021, 143, 3086-3093)
2) Peptidic Strategy for Molecular Recognition: A ratiometric fluorescent chemosensing ensemble, consisting of a macrocyclic host (cucurbituril; CB), and a pyrene‐tagged amphiphilic peptide beacon, is developed. The peptide beacon unfolds upon encapsulation of the pyrene termini into the hydrophobic CB cavity. This changes pyrene excimer to monomer emission. Analytes with a higher affinity for the CB cavity can displace peptides from the ensemble. The released peptide beacon folds again to form a pyrene excimer, which allows for the ratiometric fluorescence monitoring of the analyte. Ratiometric fluorescence monitoring of biological substrates, such as amino acid derivatives, specific peptides, and proteins, in aqueous media is demonstrated. (Chem. Eur. J., 2019, 25, 13088-13093)