Design of drugs involving receptor-ligand-DNA interactions

Details Design of drugs involving receptor-ligand-DNA interactions Design of drugs involving receptor-ligand-DNA interactions

1994-11-28

1998-01-06

Ketter, James

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving nucleic acid

364499, 514169, C12Q 168, G06F 1750, A61K 3156

Patent

active

057053359

ABSTRACT:
It has been discovered that the degree of hormonal activity of candidate ligands correlates better with degree of fit into DNA than with the strength of receptor binding, and that the receptors in the steroid/thyroid hormone/vitamin A and D family alter the physiochemical properties of DNA and in concert with other transcription factors facilitate insertion of the ligand into DNA. As a result, the magnitude of the response is a function of the structure of the ligand as it related to insertion and fit into the DNA and the specificity of the response is a function of the stereochemistry of the receptor through binding to both the ligand and to the DNA. Based on these discoveries, a method is described herein for identifying drugs having increased activity as compared with the natural ligand for receptors such as the estrogenic receptors.

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