Accession Number : ADA462061


Title :   Estrogen Receptor Driven Inhibitor Synthesis


Descriptive Note : Final rept. 1 Sep 2005-31 Aug 2006


Corporate Author : MARQUETTE UNIV MILWAUKEE WI


Personal Author(s) : Pullela, Phani K


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a462061.pdf


Report Date : Sep 2006


Pagination or Media Count : 48


Abstract : Purpose: Establish an estrogen receptor (ER) driven inhibitor synthesis procedure and develop a set of building blocks specific for ER-agonist/ER-antagonist interactions. Scope: The ER-binding pocket size is twice the molecular volume of 17-beta-estradiol (E2) giving rise to the tolerance of a diverse class of compounds resulting in poor interpretability of current SAR models. This project is to establish an ER driven ligand synthesis procedure and define a set of building blocks which cause specific agonist/antagonist interactions. Major Findings: 1) Estrone was found to react with most of the thiols to give hemi-thioketals as hypothesized in the proposal. 2) An improved synthetic route for the fluorescence polarization reagent (E2-FITC) for assay of ligands against ER was developed. 3) A database of thiols with agonist/antagonist preference for ER was developed using protein-ligand docking. 4) It was concluded that ER is not suitable protein for STD-NMR experiments due to high hydrophobicity and solubility issues. 5) NMR studies on human-ER-LBD may not be practical and use of ER from model systems like zebrafish might address the solubility issues.


Descriptors :   *ENZYMES , *PROTEINS , *ESTROGENS , *THIOLS , DATA BASES , POLARIZATION , CHEMICAL AGENTS , SOLUBILITY , HYDROPHOBIC PROPERTIES , ASSAYING , INHIBITORS , LIGANDS , FLUORESCENCE , SYNTHESIS


Subject Categories : Biochemistry
      Medicine and Medical Research
      Organic Chemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE