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Structure Elucidation of Helical Aromatic Foldamer–Protein Complexes with Large Contact Surface Areas
Author(s) -
Reddy Post Sai,
Langlois d'Estaintot Béatrice,
Granier Thierry,
Mackereth Cameron D.,
Fischer Lucile,
Huc Ivan
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201902942
Subject(s) - foldamer , chemistry , helix (gastropod) , crystallography , stereochemistry , carbonic anhydrase ii , crystal structure , carbonic anhydrase , biochemistry , enzyme , biology , ecology , snail
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.