title: Combined nuclear magnetic resonance spectroscopy and molecular dynamics study of growth hormone releasing hexapeptide GHRP-6 and a cyclic analogue.
abstract: The Growth Hormone Releasing Hexapeptide, GHRP-6 was the first of a family of synthetic peptides that enhance the release of the Growth Hormone by the pituitary gland in a dose-dependent manner. Since its discovery, it has been used as a benchmark and starting point in numerous researches aiming to obtain new drugs. Complete resonance assignment of GHRP-6 NMR spectra in both open and cyclic forms are reported, showing some differences to random coil chemical shifts. Connectivities observed in the ROESY spectra indicate spatial proximity between the aromatic residues side-chains in both molecules, as well as between residues DPhe5 and Lys6 sidechains. An ensemble of 10 structures was generated for each one of the molecules, showing RMSD values indicative of nonrandom structures. Molecular Dynamics simulations, both with and without explicit solvent, were carried out for GHRP-6 and its cyclic analogue. Conformational analysis performed on the trajectories showed a nonrandom structure with a well preserved backbone. The presence of geometrical patterns resembling those typical of π-π interactions in both peptides, suggest that this kind of interactions may be relevant for the biological activity of GHRP-6. Same conclusion can be drawn from the spatial proximity of residues DPhe5 and Lys6 sidechains.
authors.affiliation: Departamento de Química Física, Facultad de Química, Universidad de La Habana, La Habana, 10400, Cuba; Laboratorio de Química Computacional y Teórica, Facultad de Química, Universidad de La Habana, La Habana, 10400, Cuba.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fernández-Oliva
authors.forename: Héctor
authors.initials: H
authors.lastname: Santana
authors.forename: Reynier
authors.initials: R
authors.lastname: Suardíaz
authors.forename: José A
authors.initials: JA
authors.lastname: Gavín
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Pérez
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide