Self-Assembled Protein-Aromatic Foldamer Complexes with 2:3 and 2:2:1 Stoichiometries.
The 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 HCA2-23complex 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.
CBMN (UMR5248), Univ. Bordeaux, CNRS, IPB , Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33600 Pessac, France.|Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology , 50-370 Wrocław, Poland.
Michal
M
Jewginski
CBMN (UMR5248), Univ. Bordeaux, CNRS, IPB , Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33600 Pessac, France.
Thierry
T
Granier
CBMN (UMR5248), Univ. Bordeaux, CNRS, IPB , Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33600 Pessac, France.
Béatrice
B
Langlois d'Estaintot
CBMN (UMR5248), Univ. Bordeaux, CNRS, IPB , Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33600 Pessac, France.
Lucile
L
Fischer
ARNA (U 1212), Univ. Bordeaux, INSERM , Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33600 Pessac, France.
Cameron D
CD
Mackereth
CBMN (UMR5248), Univ. Bordeaux, CNRS, IPB , Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33600 Pessac, France.
Ivan
0000-0001-7036-9696
I
Huc
D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure
D006841:Hydrocarbons, Aromatic; D008024:Ligands; D002256:Carbonic Anhydrases