Synthesis and conformational studies of dipeptides constrained by disubstituted 3-(aminoethoxy)propionic acid linkers.
A series of cyclic compounds with dimethyl-substituted 3-(aminoethoxy)propionic acid linkers have been prepared as potential beta-turn mimics. The desired linkers were prepared from disubstituted pyrones, which were coupled with dipeptides and then subjected to macrocyclization using diethylcyanophosphonate to furnish cyclic compounds 1-5. Conformational analysis was carried out using NMR and X-ray crystallography. All of the five cyclic compounds were found to exist in type I or type II beta-turn conformations.
Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott Hall, Room 4070, University of Kansas, Lawrence, Kansas 66045-7582, USA.
D Srinivasa
DS
Reddy
David
D
Vander Velde
Jeffrey
J
Aubé
D003432:Cross-Linking Reagents; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011422:Propionates / Q000737:chemistry*; D011487:Protein Conformation
C484620:3-(aminoethoxy)propionic acid; D003432:Cross-Linking Reagents; D004151:Dipeptides; D010456:Peptides, Cyclic; D011422:Propionates