Accession Number:

ADA476782

Title:

Inhibitors for Androgen Receptor Activation Surfaces

Descriptive Note:

Annual rept. 1 Sep 2006-31 Aug 2007

Corporate Author:

SAN FRANCISCO UNIV CA

Personal Author(s):

• Fletterick, Robert J.

Report Date:

2007-09-01

Pagination or Media Count:

37.0

Abstract:

Studies from this grant led to discovery of a new interaction site on the androgen receptor for binding proteins that regulate the function of the receptor. The protein binders have not been identified, but we showed that the site has the characteristics of functioning in repression. We used X-ray crystallography to discover the binding mode of four compounds that bind to this site. Their binding is accompanied by weakening the interaction of the androgen receptor with coactivators as shown by disorder or representative peptides that were well ordered before adding the compounds. Thus, atomic level imaging of these interactions fit with the notion that the site functions in repression, as suggested by analysis of mutations of amino acid residues found in humans in cell and biochemical assays. This work suggests that compounds may be designed to target this site and weaken activity of the androgen receptor. Such compounds could form a new class of chemical therapeutics for treatment of prostate cancer.

Descriptors:

• *ANDROGENS
• FUNCTIONS
• ACTIVATION
• HUMANS
• INTERACTIONS
• CHEMICALS
• PEPTIDES
• BIOCHEMISTRY
• PROTEINS
• SITES
• X RAYS
• MUTATIONS
• SURFACES
• IMAGES
• THERAPY
• INHIBITORS
• BINDERS
• ASSAYING
• PROSTATE CANCER
• RESIDUES
• SENSE ORGANS
• AMINO ACIDS
• CRYSTALLOGRAPHY
• ATOMIC ENERGY LEVELS

Subject Categories:

• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE