This proposal is designed to develop a potent beta-turn mimetic endothelin antagonist via directed combinatorial synthesis, and to evaluate the bioactive solution conformation of the antagonist. Endothelin, a 21 amino acid peptide, is a member of a group of important biomolecules which adopt a beta-turn conformation in solution. The proposed mimetic class contains a thioether linker to restrict the turn conformation, has three sidechains to enhance receptor binding, and has greater bioavailability than peptide antagonists. A combinatorial library will be synthesized, assayed for affinity, and the solution conformation of the strongest antagonists will be determined. A second library will then be synthesized, with components chosen to promote the probable bioactive conformer identified in the previous analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM018287-02
Application #
2608716
Study Section
Special Emphasis Panel (ZRG3-BNP (02))
Project Start
1997-11-16
Project End
Budget Start
1997-11-16
Budget End
1998-10-15
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704