Conformationally stable and constrained macrocarbocyclic pseudopeptide mimics of beta-hairpin structures.
Subjecting a D-Pro-L-Pro template harboring N- and C-terminal omega-alkenyl amino acids to a ring-closure metathesis reaction afforded the corresponding macrocyclic alkenes. A cis-alkene analogue crystallized with one molecule each of water and chloroform, which were retained even after heating at 100 degrees C. By using the reduced macrocyclic product as a template, the metathesis could be repeated twice on newly installed omega-alkenyl amino acids to give three-tiered macrocarbocyclic pseudopeptides as mixtures of conformers. NMR studies revealed the high conformational stability of these motifs.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, QC, Canada. stephen.hanessian@umontreal.ca
Angiolini
Mauro
M
D000475:Alkenes / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D002845:Chromatography; D003500:Cyclization; D004151:Dipeptides / Q000737:chemistry; D006865:Hydrogenation; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D011487:Protein Conformation; D011725:Pyridines / Q000737:chemistry; D013696:Temperature
D000475:Alkenes; D000596:Amino Acids; D004151:Dipeptides; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011725:Pyridines; C448039:prolyl-proline; C023666:pyridine