Characterizing the Dynamic Response of the Estrogen Receptor to Agonists and Antagonists by Multi-frequency Electron Spin Resonance Spin-Labeling

Abstract

The overall objective of this project is to characterize the detailed structural and dynamic response of the estrogen receptor ligand binding domain (ER-LBD) to a variety of ligands ranging from strong estrogens to strong antiestrogens using electron spin labeling. The technical aims for the initial period involved developing site-directed spin-labeled mutants of the ER-LBD and synthesizing new spin-labeled ligands for the proposed studies. We have optimized cell culture production of ER-LBD and expressed a number of single and doubly labeled mutants. In addition we have synthesized a new spin label for attachment to site-selected cysteine residues in this protein and made substantial progress towards the synthesis of spin-labeled ligands with a range of agonist/antagonist activities. Initial electron spin resonance studies have established that the selected label locations will be acceptably sensitive to the type of ligand present.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2007
Accession Number
ADA472067

Entities

People

  • David E. Budil
  • Robert N. Hanson

Organizations

  • Northeastern University

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Analytical Chemistry
  • Attachment
  • Chemical Compounds
  • Chemistry
  • Crystal Structure
  • Culture Techniques
  • Cysteine
  • Dynamic Response
  • Electron Spin Resonance
  • Electrons
  • Estrogens
  • Free Radicals
  • Frequency
  • Production
  • Resonance
  • Spin Resonance

Fields of Study

  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry
  • Quantum spin resonance or Electron Paramagnetic Resonance spectroscopy.

Technology Areas

  • Microelectronics