In response to increasing awareness of the suspected role of estrogen mimics in reproductive disorders and cancer, during Phase I work, the investigators demonstrated the feasibility of developing a fiber optic sensor for screening estrogen mimics. The instrument reports rapid real-time data on binding between biological macromolecules and their ligands. Sensor measurements performed on several estrogens and mimics were well correlated with conventional affinity measurements for those compounds. By combining information obtained from two different types of fibers, the sensors distinguished between strong and weak estrogens and between estrogenic agonists and an estrogenic antagonist, reflecting strong agreement between sensor results and bioactivity. A patent and three publications are in preparation as a result of this work. Proposed Phase II work will entail: 1) optimization of chemical and molecular biological methods and protocols, 2) refinements in mathematical methods, 3) prototype design and construction, and 4) validation with blind samples of estrogen mimics. The resulting instrument and stabilized reagents provide a rapid assessment of estrogenic and endocrine disrupting potential of samples. This approach may be adapted to pharmaceutical development and identification of non- estrogenic compounds with endocrine-disrupting properties.
Agencies monitoring environmental estrogen mimics and screening compounds for estrogenic endocrine disrupting potential, industries monitoring their own waste streams for pseudo-estrogens, pharmaceutical companies seeking anti-breast cancer agents by screening compounds for binding to the estrogen receptor or determining real time binding constants of substances for biomolecules, researchers studying mechanisms of signal transduction.