Issue 48, 2024

Interrogating the potential of helical aromatic foldamers for protein recognition

Abstract

A biotinylated helical aromatic oligoamide foldamer equivalent in size to a 24mer peptide was designed without any prejudice other than to display various polar and hydrophobic side chains at its surface. It was synthesized on solid phase, its P- and M-helical conformers were separated by HPLC on a chiral stationary phase, and the solid state structure of a non-biotinylated analogue was elucidated by X-ray crystallography. Pull-down experiments from a yeast cell lysate using the foldamer as a bait followed by proteomic analysis revealed potential protein binding partners. Three of these proteins were recombinantly expressed. Biolayer interferometry showed submicromolar binding demonstrating the potential of a given foldamer to have affinity for certain proteins in the absence of design considerations. Yet, binding selectivity was low in all three cases since both P- and M-conformers bound to the proteins with similar affinities.

Graphical abstract: Interrogating the potential of helical aromatic foldamers for protein recognition

  • This article is part of the themed collection: Foldamers

Supplementary files

Article information

Article type
Communication
Submitted
02 Sep 2024
Accepted
29 Oct 2024
First published
30 Oct 2024
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2024,22, 9342-9347

Interrogating the potential of helical aromatic foldamers for protein recognition

S. Kwon, V. Morozov, L. Wang, P. K. Mandal, S. Chaignepain, C. Douat and I. Huc, Org. Biomol. Chem., 2024, 22, 9342 DOI: 10.1039/D4OB01436G

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