Work

Structure Elucidation of Helical Aromatic Foldamer–Protein Complexes with Large Contact Surface Areas

Year: 2019

Type: article

Abstract: The development of large synthetic ligands could be useful to target the sizeable surface areas involved in protein–protein interactions. Herein, we present long helical aromatic oligoamide foldamers bearing proteinogenic side chains that cover up to 450 Å 2 of the human carbonic anhydrase II (HCA) surface. The foldamers are composed of aminoquinolinecarboxylic acids bearing proteinogenic side chains and of more flexible aminomethyl‐pyridinecarboxylic acids that enhance helix handedness dynamics. Crystal structures of HCA‐foldamer complexes were obtained with a 9‐ and a 14‐mer both showing extensive protein–foldamer hydrophobic contacts. In addition, foldamer–foldamer interactions seem to be prevalent in the crystal packing, leading to the peculiar formation of an HCA superhelix wound around a rod of stacked foldamers. Solution studies confirm the positioning of the foldamer at the protein surface as well as a dimerization of the complexes.

Source: Chemistry - A European Journal

DOI: 10.1002/chem.201902942

Authors: Post Sai Reddy, Béatrice Langlois d'Estaintot, Thierry Granier, Cameron D. Mackereth, Lucile Fischer, Ivan Huc