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


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a476782.pdf


Report Date : Sep 2007


Pagination or Media Count : 37


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