Measurement of the Electron Density Distribution of Estrogens-A First Step to Advanced Drug Design
Abstract
Estrogen derivatives bind as ligands to the estrogen receptor initiating biological reactions, which can cause either initiation/progress or inhibition of tumor growth. Slight structural variations in these molecules can change their carcinostatic potentials from agonistic to inhibitory. The principle objective of this proposal is to relate known biological reactions to physical properties such as point charges of atoms and the electrostatic potential. We are obtaining information about these electronic properties of estrogen derivatives from experimental determination of their electron density using high quality single crystal X-ray crystallography. We derived electron density, electrostatic potential and related properties for six estrogen crystals. We have developed the methodology of the X-ray CCD data treatment and least-squares model refinement in order to extract maximum reliable information from the data. We found that the deformation electron density distributions of all hydroxyl oxygen atoms are near sp3 in shape, their lone pair densities have been reliably located. These configurations as well as the electrostatic potentials around the oxygen atoms are very consistent in 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA409631
Entities
People
- Alan A. Pinkerton
Organizations
- University of Toledo