3D PHARMACOPHORE FOA THE DESIGN OF HUMAN POLY ADENOSINE RIBONUCLEASE (PARN) INHIBITORS

摘要

The present invention relates to means and methods for the design of highly specific anti-PARN agent using our 3D pharmacophore. Using a library of previously published modified nucleoside analog substrates acting in the proximity of the scissile bond of PARN, we conducted structure - activity relationship (SAR) analysis, structural characterization and complex (receptor-ligand) based molecular dynamics simulations that led to the design of a PARN-specific pharmacophore. Our full pharmacophore consists of five pharmacophoric annotation points, which include two hydrogen donating PAPs, one hydrophobic PAP, one aromatic PAP and a hydrogen accepting PAP, in the vicinity of human poly-Adenosine ribonuclease catalytic site.