Amphipathic helices from aromatic amino acid oligomers.
Synthetic helical foldamers are of significant interest for mimicking the conformations of naturally occurring molecules while at the same time introducing new structures and properties. In particular, oligoamides of aromatic amino acids are attractive targets, as their folding is highly predictable and stable. Here the design and synthesis of new amphipathic helical oligoamides based on quinoline-derived amino acids having either hydrophobic or cationic side chains are described. Their structures were characterized in the solid state by single-crystal X-ray diffraction and in solution by NMR. Results of these studies suggest that an oligomer as short as a pentamer folds into a stable helical conformation in protic solvents, including MeOH and H(2)O. The introduction of polar proteinogenic side chains to these foldamers, as described here for the first time, promises to provide possibilities for the biological applications of these molecules. In particular, amphipathic helices are versatile targets to explore due to their importance in a variety of biological processes, and the unique structure and properties of the quinoline-derived oligoamides may allow new structure-activity relationships to be developed.
Gillies
Elizabeth R
ER
Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac Cedex, France.
Dolain
Christel
C
Léger
Jean-Michel
JM
Huc
Ivan
I
D024322:Amino Acids, Aromatic / Q000737:chemistry*; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011804:Quinolines; D012997:Solvents; D013329:Structure-Activity Relationship
D024322:Amino Acids, Aromatic; D009842:Oligopeptides; D011804:Quinolines; D012997:Solvents; C037219:quinoline