Structure Elucidation of Helical Aromatic Foldamer-Protein Complexes with Large Contact Surface Areas
Langue
EN
Article de revue
Ce document a été publié dans
Chemistry-a European Journal. 2019, vol. 25, p. 11042-11047
Résumé en anglais
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 ...Lire la suite >
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 angstrom(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.< Réduire
Mots clés en anglais
aromatic oligoamides
foldamers
protein surface recognition
structure elucidation
X-ray crystallography
Unités de recherche