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

• Type: Article in International Scientific Journal
• Date: 2005

Authors

Pande, V (Author) Other; Ramos, MJ (Author) FCUP

Journal

Title: Bioorganic and Medicinal Chemistry Letters

Vol. 15 No. 6

Pages: 4057-4063

ISSN: 0960-894X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 36 Citations

Scopus - 38 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: 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).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7