I. The Development of Estrogen Receptor Coactivator Binding Inhibitors. II. Investigations Into the Binding Modes of Ligands Selective for Estrogen Receptor Alpha

Rodriguez, Alice Lambert

Permalink

https://hdl.handle.net/2142/84106 Copy

Description

Title

I. The Development of Estrogen Receptor Coactivator Binding Inhibitors. II. Investigations Into the Binding Modes of Ligands Selective for Estrogen Receptor Alpha

Author(s)

Rodriguez, Alice Lambert

Issue Date

2003

Doctoral Committee Chair(s)

Katzenellenbogen, John A.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Biology, Molecular

Language

eng

Abstract

Our laboratory has previously discovered that certain heterocycles show high binding affinity and selectivity for ERalpha. In order to design more potent and selective derivatives, a better understanding of how they bind to the receptor is needed. Using a comparative binding analysis method and molecular modeling, we were able to assess the binding mode of a furan agonist and antagonist. As an agonist, the furan binds to the receptor with the C(2) phenol acting as the A-ring in most cases. As an antagonist, the furan binds with the C(5) phenol acting as the A-ring mimic and the basic side chain extending back into the pocket in a similar fashion to known antagonists. The preparation of various mono and bisphenolic furan analogs in conjunction with molecular modeling assisted in confirming these assertions.

Graduation Semester

2003

Type of Resource

text

Permalink

http://hdl.handle.net/2142/84106

Owning Collections