Investigation of solvent effect and NMR shielding tensors of p53 tumor-suppressor gene in drug design

S Irani1, M Monajjemi2, B Honarparvar2, SM Atyabi3, M Sadeghizadeh41Department of Biology, 2Department of Chemistry, 3Department of Medical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran; 4Department of Genetics, School of Biological Sciences, Tarbiat Modares Univers...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: S Irani, M Monajjemi, B Honarparvar, et al
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2011
Materias:
Acceso en línea:https://doaj.org/article/ad9e1365dc3d4699806c0ea380cd006d
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:S Irani1, M Monajjemi2, B Honarparvar2, SM Atyabi3, M Sadeghizadeh41Department of Biology, 2Department of Chemistry, 3Department of Medical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran; 4Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, IranAbstract: The p53 tumor-suppressor gene encodes a nuclear phosphoprotein with cancer-inhibiting properties. The most probable cancerous mutations occur as point mutations in exons 5 up to 8 of p53, as a base pair substitution that encompasses CUA and GAT sequences. As DNA drug design represents a direct genetic treatment of cancer, in the research reported computational drug design was carried out to explore, at the Hartree–Fock level, effects of solvents on the thermochemical properties and nuclear magnetic resonance (NMR) shielding tensors of some atoms of CUA involved in the hydrogen-bonding network. The observed NMR shielding variations of the solutes caused by solvent change seemed significant and were attributed to solvent polarity, and solute–solvent and solvent–solute hydrogen-bonding interactions. The results provide a reliable insight into the nature of mutation processes. However, to improve our knowledge of the hydration pattern more rigorous computations of the hydrated complexes are needed.Keywords: p53, CUA, mutation, ab initio method, NMR shielding