Design, synthesis, and conformational analysis of trispyrimidonamides as α-helix mimetics.
The straightforward synthesis of trispyrimidonamides as a new class of α-helix mimetics is reported. Because of the versatility of our synthetic protocol, a variety of side chains including aliphatic, basic, aromatic, and heteroaromatic residues were included. A comprehensive conformational analysis revealed that in polar solvents a trimeric compound adopts conformations that can lead to i, i + 4, i + 8, or i, i + 8 patterns of side chain orientation. This suggests that trispyrimidonamides could be promising α-helix mimetics to target hot spots that are distributed over a wider angular range of an α-helix interface than in the classical i, i + 4, i + 7 case.
Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universität Düsseldorf , Universitätsstr. 1, 40225 Düsseldorf, Germany.
Lukas
L
Spanier
Emanuele
E
Ciglia
Finn K
FK
Hansen
Krystina
K
Kuna
Walter
W
Frank
Holger
H
Gohlke
Thomas
T
Kurz
D000596:Amino Acids / Q000737:chemistry*; D032701:Biomimetics; D008968:Molecular Conformation; D017433:Protein Structure, Secondary; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry; D012997:Solvents
D000596:Amino Acids; D011744:Pyrimidinones; D012997:Solvents