Measurement of the Electron Density Distribution of Estrogens - A First Step to Advanced Drug Design
Abstract
Estrogens bind as ligands to the estrogen receptor initiating biological reactions, which can cause either initiation/progress or inhibition of tumor growth. The principle objective of this proposal was to relate known biological reactions to ligand physical properties such as the electrostatic potential. We have demonstrated the ability to determine the experimental electron potential. We have demonstrated the ability to determine the experimental electron density distribution and electrostatic potential of larger molecular systems such as estrogens. We have developed the methodology of crystallization, the x-ray CCD data treatment and least-squares model refinement procedure for estrogen crystals in order to extract maximum reliable and comparable information from the data. We completed charge density studies of six estrogen derivatives, performed the preliminary analysis and compared the results. We found that the electron density concentration associated with oxygen lone pairs are near sp3 in shape. These configurations as well as the electroscopic potentials are very consistent I the different hydrogen bonding environments. The core estrogen structure is also very consistent between the derivatives. The significant differences are found at the activity-sensitive molecular parts. In order to reliably associate the molecular recognition of a drug molecule to receptor with an electrostatic potential, a bigger data base of charge densities for estrogen molecules has to be built.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA418932
Entities
People
- Alan A. Pinkerton
Organizations
- University of Toledo