Self-Assembled Protein–Aromatic Foldamer Complexes with 2:3 and 2:2:1 Stoichiometries
dataset
posted on 2017-02-07, 00:00 authored by Michal Jewginski, Thierry Granier, Béatrice Langlois d’Estaintot, Lucile Fischer, Cameron D. Mackereth, Ivan HucThe promotion of
protein dimerization using the aggregation properties
of a protein ligand was explored and shown to produce complexes with
unusual stoichiometries. Helical foldamer 2 was synthesized
and bound to human carbonic anhydrase (HCA) using a nanomolar active
site ligand. Crystal structures show that the hydrophobicity of 2 and interactions of its side chains lead to the formation
of an HCA2-23 complex in which
three helices of 2 are stacked, two of them being linked
to an HCA molecule. The middle foldamer in the stack can be replaced
by alternate sequences 3 or 5. Solution
studies by CD and NMR confirm left-handedness of the helical foldamers
as well as HCA dimerization.
