Estrogen Receptor Driven Inhibitor Synthesis

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.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2006
Accession Number
ADA462061

Entities

People

  • Phani K. Pullela

Organizations

  • Marquette University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Alcohols
  • Amino Acids
  • Cells
  • Cellular Structures
  • Chemical Compounds
  • Chemical Reactions
  • Chemical Synthesis
  • Chemistry
  • Department Of Defense
  • Enzyme Inhibitors
  • Fish
  • Medical Personnel
  • Organic Chemistry
  • Small Molecules

Fields of Study

  • Chemistry

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