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Solution Observation of Dimerization and Helix Handedness Induction in a Human Carbonic Anhydrase–Helical Aromatic Amide Foldamer Complex
Author(s) -
Jewginski Michal,
Fischer Lucile,
Colombo Cinzia,
Huc Ivan,
Mackereth Cameron D.
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500619
Subject(s) - foldamer , chemistry , dimer , helix (gastropod) , carbonic anhydrase , amide , carbonic anhydrase ii , stereochemistry , enantiomer , crystallography , biochemistry , enzyme , biology , ecology , organic chemistry , snail
The design of synthetic foldamers to selectively bind proteins is currently hindered by the limited availability of molecular data to establish key features of recognition. Previous work has described dimerization of human carbonic anhydrase II (HCA) through self‐association of a quinoline oligoamide helical foldamer attached to a tightly binding HCA ligand. A crystal structure of the complex provided atomic details to explain the observed induction of single foldamer helix handedness and revealed an unexpected foldamer‐mediated dimerization. Here, we investigated the detailed behavior of the HCA–foldamer complex in solution by using NMR spectroscopy. We found that the ability to dimerize is buffer‐dependent and uses partially distinct intermolecular contacts. The use of a foldamer variant incapable of self‐association confirmed the ability to induce helix handedness separately from dimer formation and provided insight into the dynamics of enantiomeric selection.