14-helical folding in a cyclobutane-containing beta-tetrapeptide.
The efficient synthesis of tetrapeptide 5 containing, in alternation, cyclobutane and beta-alanine residues is described. NMR experiments both at low temperature in CDCl(3) and at 298 K in DMSO-d(6) solutions show the contribution of a strong hydrogen bond in the folded major conformation of 5. Temperature coefficients and diffusion times point out a hydrogen bond involving the NH proton from the cyclobutane residue 1 whereas NOEs manifest the high rigidity of the central fragment of the molecule and are compatible with a 14-membered macrocycle. Theoretical calculations predict a most stable folded conformation corresponding to a 14-helix stabilized by a hydrogen bond between NH(10) in the first residue and OC(25) in the third residue. This structure remains unaltered during the molecular dynamics simulation at 298 K in chloroform. All these results provide evidence for a 14-helical folding and reveal the ability of cis-2-aminocyclobutane carboxylic acid residues to promote folded conformations when incorporated into beta-peptides.
Izquierdo
Sandra
S
Departament de Química, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Kogan
Marcelo J
MJ
Parella
Teodor
T
Moglioni
Albertina G
AG
Branchadell
Vicenç
V
Giralt
Ernest
E
Ortuño
Rosa M
RM
D003503:Cyclobutanes / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
D003503:Cyclobutanes; D009842:Oligopeptides