The immediate goal of the proposed research is to explore and develop the chemistry of new host molecules with multiple, interactive recognition sites. Central to this purpose is the synthesis of crown ethers and cyclophanes appended to a metallocene. The free rotation of metallocenes about their central axis will allow them to communicate conformational information from one recognition site to another. This interdependence of recognition site conformations will manifest itself experimentally in allosteric binding behavior. That is, the binding of the first guest will organize the remote binding site so as to favor or disfavor the binding of the second guest; these effects are termed positive and negative cooperativity, respectively. Metallocenes will also accommodate a wide array of auxillary functional groups. Thus, electrostatic and steric forces may be exploited in the design of these allosteric systems. The findings of the proposed research will serve to delineate the concepts that underly allosteric interactions in enzymes, receptors, and other cellular machinery, as well as synthetic systems including """"""""molecular devices.""""""""

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM039816-02
Application #
3297030
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1988-09-01
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Arts and Sciences
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213