During Phase I, IA Inc. and HRL developed a novel, regenerable, fiber optic biosensor for monitoring in real-time, molecular interactions between estrogen receptor modulators and both hER-alpha and hER-beta. These biosensors don't require fluorophore labeling of receptor, are more specific than sensors monitoring mass on the sensor surface, and utilize only 10 femtomoles of receptor per sample. Sensors provide a kinetic association and dissociation curve for a compound in 9-10 minutes. Sensor data on the interaction between a variety of xeno-, phyto- and endogenous estrogens and hER-alpha or hER-beta generally agrees with previously reported binding studies. Exciting new data was also obtained. Of particular significance is the observation that genistein, a phytoestrogen believed to be protective against certain cancers, produces a greater increase in stable complex formation between ERE and hER-beta than it does with hER-alpha. Also diethyl phthalate, a compound widely used in colognes and cosmetics, selectively activates formation of stable complex between ERE and hER-alpha but not hER-beta. Phase II work will develop a prototype instrument and further explore the possibility of distinguishing between beneficial and harmful estrogen receptor modulators by kinetic measurements using hER-alpha and hER-beta.

Proposed Commercial Applications

Not Available

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44ES010076-03
Application #
6525218
Study Section
Special Emphasis Panel (ZRG1-BCE (10))
Program Officer
Heindel, Jerrold
Project Start
1999-09-30
Project End
2004-09-29
Budget Start
2002-09-30
Budget End
2004-09-29
Support Year
3
Fiscal Year
2002
Total Cost
$349,658
Indirect Cost
Name
IA, Inc.
Department
Type
DUNS #
City
Dexter
State
MI
Country
United States
Zip Code
48130
Andres, Sarah A; Bumpus, Stefanie B; Wittliff, James L (2013) Assessment of phytoestrogen and mycoestrogen recognition by recombinant human estrogen receptor-? using ligand titration arrays. Phytochem Anal 24:357-66
Wittliff, James L; Andres, Sarah A; Kruer, Traci L et al. (2008) Biosensors for detecting estrogen-like molecules and protein biomarkers. Adv Exp Med Biol 614:315-22
Andres, Sarah A; Kerr 2nd, D Alan; Bumpus, Stefanie B et al. (2008) A three-tiered approach for calibration of a biosensor to detect estrogen mimics. Adv Exp Med Biol 614:305-13