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Structure of a Complex Formed by a Protein and a Helical Aromatic Oligoamide Foldamer at 2.1 Å Resolution
Author(s) -
Buratto Jérémie,
Colombo Cinzia,
Stupfel Marine,
Dawson Simon J.,
Dolain Christel,
Langlois d'Estaintot Béatrice,
Fischer Lucile,
Granier Thierry,
Laguerre Michel,
Gallois Bernard,
Huc Ivan
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201309160
Subject(s) - foldamer , chemistry , helix (gastropod) , crystallography , circular dichroism , stereochemistry , ligand (biochemistry) , monomer , molecule , carbonic anhydrase ii , carbonic anhydrase , biochemistry , enzyme , organic chemistry , polymer , biology , receptor , ecology , snail
In the search of molecules that could recognize sizeable areas of protein surfaces, a series of ten helical aromatic oligoamide foldamers was synthesized on solid phase. The foldamers comprise three to five monomers carrying various proteinogenic side chains, and exist as racemic mixtures of interconverting right‐handed and left‐handed helices. Functionalization of the foldamers by a nanomolar ligand of human carbonic anhydrase II (HCA) ensured that they would be held in close proximity to the protein surface. Foldamer–protein interactions were screened by circular dichroism (CD). One foldamer displayed intense CD bands indicating that a preferred helix handedness is induced upon interacting with the protein surface. The crystal structure of the complex between this foldamer and HCA could be resolved at 2.1 Å resolution and revealed a number of unanticipated protein–foldamer, foldamer–foldamer, and protein–protein interactions.