Measurement of the Electron Density Distribution of Estrogens-A First Step to Advanced Drug Design
Abstract
Estradiol and related compounds 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 principal 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. With the completion of the first electron density experiment of an estradiol derivative, we have proven, that the technique will indeed work for molecules of this magnitude. We have determined the electrostatic potential and related properties for estrogen. Further data sets of 17 alpha-estradiol.l/2 H20 and l7 beta- estradiol.l/2 MeOH have been collected and are under investigation. Comparison of electronic properties of several estrogen derivatives is essential in order to identify certain regions of the electrostatic potential of a ligand that can be related to biological functionality. Furthermore, we solved the X-ray structures of three new crystal modifications of estradiol derivatives, which add to the overall knowledge about estradiols.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA385441
Entities
People
- Alan Pinkerton
Organizations
- University of Toledo