Abstract

This application proposes to 1) design and synthesize affinity labels for the AR; 2) characterize the binding and pharmacological activities of the synthesized compounds; and 3) synthesize radiolabelled versions of promising compounds and employ them as affinity labels. The studies outlined in the final two specific aims are designed to demonstrate the irreversibility of binding and to identify the amino acids to which these compounds have been linked.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA068096-06
Application #
6376167
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Forry, Suzanne L
Project Start
1997-09-01
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2003-08-31
Support Year
6
Fiscal Year
2001
Total Cost
$108,753
Indirect Cost

  Institution

Name
Ohio State University
Department
Type
Schools of Pharmacy
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Wu, Zengru; Gao, Wenqing; Phelps, Mitch A et al. (2004) Favorable effects of weak acids on negative-ion electrospray ionization mass spectrometry. Anal Chem 76:839-47
Yin, Donghua; He, Yali; Perera, Minoli A et al. (2003) Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor. Mol Pharmacol 63:211-23
Zhu, Z; Bulgakov, O V; Scott, S S et al. (2001) Recombinant expression and purification of human androgen receptor in a baculovirus system. Biochem Biophys Res Commun 284:828-35
Zhu, Z; Becklin, R R; Desiderio, D M et al. (2001) Mass spectrometric characterization of the human androgen receptor ligand-binding domain expressed in Escherichia coli. Biochemistry 40:10756-63
Zhu, Z; Becklin, R R; Desiderio, D M et al. (2001) Identification of a novel phosphorylation site in human androgen receptor by mass spectrometry. Biochem Biophys Res Commun 284:836-44
Marhefka, C A; Moore 2nd, B M; Bishop, T C et al. (2001) Homology modeling using multiple molecular dynamics simulations and docking studies of the human androgen receptor ligand binding domain bound to testosterone and nonsteroidal ligands. J Med Chem 44:1729-40
Kirkovsky, L; Mukherjee, A; Yin, D et al. (2000) Chiral nonsteroidal affinity ligands for the androgen receptor. 1. Bicalutamide analogues bearing electrophilic groups in the B aromatic ring. J Med Chem 43:581-90
Mukherjee, A; Kirkovsky, L I; Kimura, Y et al. (1999) Affinity labeling of the androgen receptor with nonsteroidal chemoaffinity ligands. Biochem Pharmacol 58:1259-67