Molecular recognition of 15-deoxy-Delta(12,14)-prostaglandin J(2) by nuclear factor-kappa B and other cellular proteins

• Tipo: Artigo em Revista Científica Internacional
• Data: 2005

Autores

Pande, V (Autor) Outra; Ramos, MJ (Autor) FCUP

Revista

Título: Bioorganic and Medicinal Chemistry Letters

Vol. 15 Nº 6

Páginas: 4057-4063

ISSN: 0960-894X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 36 Citações

Scopus - 38 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-000-1BP

DOI: 10.1016/j.bmcl.2005.06.025

Abstract (EN): 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a dehydration product of prostaglandin D-2, is an important pharmacological molecule, which with the virtue of its electrophilicity, has been reported to covalently modify some cellular proteins (such as nuclear factor-kappa B (NF-kappa B), AP-1, p53, and thioredoxin) and elicit its physiological effects. The aim of the present computational study is to understand the role molecular recognition plays in the association of 15d-PGJ(2) with NF-kappa B and other proteins. Another aim is to characterize whether p53 is a direct target for covalent modification by 15d-PGJ(2). A docking strategy is applied along with calculation of ab initio electrostatic potential maps to analyze the mode of binding of prostaglandin molecule with critical cysteine-containing sites in each protein. The results provide identification of important sites in the target proteins, which provide recognition and stability to the prostaglandin molecule. Fit of shape and complementarity of electrostatic interactions are derived as significant determinants of molecular recognition of 15d-PGJ(2). Further, comparative results indicate that p53 protein may also be a target for direct modification by 15d-PGJ(2). The molecular models obtained should allow the rational design of more specific analogs of 15d-PGJ(2).

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7