Synthesis of conformationally constrained peptidomimetics using multicomponent reactions.
A novel modular synthetic approach toward constrained peptidomimetics is reported. The approach involves a highly efficient three-step sequence including two multicomponent reactions, thus allowing unprecedented diversification of both the peptide moieties and the turn-inducing scaffold. The turn-inducing properties of the dihydropyridone scaffold were evaluated by molecular modeling, X-ray crystallography, and NMR studies of a resulting peptidomimetic. Although modeling studies point toward a type IV beta-turn-like structure, the X-ray crystal structure and NMR studies indicate an open turn structure.
Scheffelaar
Rachel
R
Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Nijenhuis
Roel A Klein
RA
Paravidino
Monica
M
Lutz
Martin
M
Spek
Anthony L
AL
Ehlers
Andreas W
AW
de Kanter
Frans J J
FJ
Groen
Marinus B
MB
Orru
Romano V A
RV
Ruijter
Eelco
E
D040761:Biomimetic Materials / Q000737:chemistry*; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D013696:Temperature
D010455:Peptides