Phosphoramidate derivatives of hydroxysteroids as inhibitors of prostate-specific membrane antigen

WCC 23

Lisa Yong Wu, lisawu44@yahoo.com1, Jacinda Do1, Marat Kazak1, Helen Page1, Yoko Toriyabe2, Marc O. Anderson1, and Clifford E. Berkman, cberkman@sfsu.edu1. (1) Chemistry & Biochemistry, San Francisco State University, 1600 Holloway Ave., San Francisco, CA 94132, (2) Chemistry and Biochemistry, San Francisco State Univeristy, 1600 Holloway Ave., San Francisco, CA 94132
Prostate-specific membrane antigen (PSMA) is a membrane-bound cell surface peptidase which is over-expressed in prostate cancer cells. The enzymatic activities of PSMA are understood but the role of the enzyme in healthy and diseased states remains conjectural. We previously confirmed the existence of a hydrophobic binding site remote from the enzyme's catalytic center. To explore the specificity of this binding site, we prepared a series of six glutamate-containing phosphoramidate derivatives of various hydroxysteroids. The inhibitory potency of the individual compounds of the series was comparable to a simple hydrophobic analog, and in all cases IC50 values were sub-micromolar. Molecular docking was used to develop a model to explain the relative inhibitory potencies of the compounds examined.
 

Many Faces of Chemistry: Merck Index Women in Chemistry
1:00 PM-3:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Poster

Women Chemists Committee

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007