SFB 1309
Interrogating the potential of helical aromatic foldamers for protein recognition
2024-10-29
Sunbum Kwon, Vasily Morozov, Lingfei Wang, Pradeep K. Mandal, Stéphane Chaignepain, Céline Douat and Ivan Huc
Org. Biomol. Chem., 2024, 22, 9342
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.
