I. Design and synthesis of estrogen receptor gene switches. II. Design and synthesis of estrogen receptor ligands occupying an auxiliary binding pocket
Comninos, John
Loading…
Permalink
https://hdl.handle.net/2142/29812
Description
Title
I. Design and synthesis of estrogen receptor gene switches. II. Design and synthesis of estrogen receptor ligands occupying an auxiliary binding pocket
Author(s)
Comninos, John
Issue Date
2012-02-06T20:18:35Z
Director of Research (if dissertation) or Advisor (if thesis)
The estrogen receptor (ER) is ligand-regulated nuclear hormone receptor and an important therapeutic target for breast cancer, hormone replacement therapy, contraception, and osteoporosis. Novel organic cores have been identified and developed as possible estrogen pharmaceuticals. The x-ray structures of both estrogen receptor subtypes bound to unique ligands provide a way to interpret, improve, and/or design estrogen ligands using computer modeling.
Novel synthetic estrogen ligands were designed using computer modeling to occupy a solvent channel present in all of the ER crystal structures, although those ligands bound poorly to the estrogen receptor. Also, single mutations of ER residues near the ligand binding pocket were evaluated using modeling to predict the size and shape of the mutated binding pocket that would not bind estradiol. Ligands were designed, synthesized, and tested using a yeast two-hybrid assay to activate the mutated receptor to near wild type activity and create a novel gene switch.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
