14-Helical folding in a cyclobutane-containing β-tetrapeptide

The efficient synthesis of tetrapeptide 5 containing, in alternation, cyclobutane and β-alanine residues is described. NMR experiments both at low temperature in CDCl3 and at 298 K in DMSO-d6 solutions show the contribution of a strong hydrogen bond in the folded major conformation of 5. Temperature...

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Detalles Bibliográficos
Autores: Izquierdo, Sandra, Kogan, Marcelo Javier, Parella, Teodor, Moglioni, Albertina Gladys, Branchadell, Vicenc, Giralt, Ernest, Ortuño, Rosa M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2004
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/137894
Acceso en línea:http://hdl.handle.net/11336/137894
Access Level:acceso abierto
Palabra clave:helical folding
peptides
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario:The efficient synthesis of tetrapeptide 5 containing, in alternation, cyclobutane and β-alanine residues is described. NMR experiments both at low temperature in CDCl3 and at 298 K in DMSO-d6 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 NH10 in the first residue and OC25 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 β-peptides.