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Chembiochem. 2016 Apr 15;17(8):727-36. doi: 10.1002/cbic.201500619. Epub 2016 Mar 4.

Solution Observation of Dimerization and Helix Handedness Induction in a Human Carbonic Anhydrase-Helical Aromatic Amide Foldamer Complex.

Jewginski M1,2,3,4, Fischer L1,2,3, Colombo C1,2,3, Huc I5,6,7, Mackereth CD8,9,10.

Author information

1
University of Bordeaux, CBMN (UMR 5248), Institut Européen de Chimie et Biologie, 2 rue Escarpit, 33600, Pessac, France.
2
CNRS, CBMN (UMR 5248).
3
Bordeaux Institut National Polytechnique, CBMN (UMR 5248).
4
Wrocław University of Technology, Faculty of Chemistry, Wrocław, Poland.
5
University of Bordeaux, CBMN (UMR 5248), Institut Européen de Chimie et Biologie, 2 rue Escarpit, 33600, Pessac, France. i.huc@iecb.u-bordeaux.fr.
6
CNRS, CBMN (UMR 5248). i.huc@iecb.u-bordeaux.fr.
7
Bordeaux Institut National Polytechnique, CBMN (UMR 5248). i.huc@iecb.u-bordeaux.fr.
8
University of Bordeaux, ARNA (U1212), Institut Européen de Chimie et Biologie. c.mackereth@iecb.u-bordeaux.fr.
9
INSERM, ARNA (U1212). c.mackereth@iecb.u-bordeaux.fr.
10
CNRS, ARNA (UMR 5320), 2 rue Escarpit, 33600, Pessac, France. c.mackereth@iecb.u-bordeaux.fr.

Abstract

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.

KEYWORDS:

circular dichroism; foldamers; human carbonic anhydrase; molecular recognition; nuclear magnetic resonance

PMID:
26807531
DOI:
10.1002/cbic.201500619
[Indexed for MEDLINE]

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