The long-term goal of this project is to define the structure-function relationships of pituitary growth hormone, HCS(hPL) and related proteins. The current proposal seeks to exploit the physico-chemical differences between hGH and HCS (hPL) with the intent of sorting out those aspects which specifically prevent HCS (hPL) from being a potent growth promoting agent. New optical techniques will be used to search the native molecules for additional differences. Non-covalent recombinants (complementation reactions) will be employed to establish precisely which residues between sequence positions 135 and 191 are responsible for interacting with the first 134 residues to create the Alpha-helix content and micro-environments of Trp86 and Tyr143, characteristic of each molecule. Conformational similarities between hGH and HCS (hPL) will be correlated with known prolactin conformations in order to establish which are responsible for the nearly equivalent lactogenic potencies of these molecules. Similarly, elephant growth hormone will be isolated and its conformation studied to further identify secondary and tertiary structural characteristics which are highly conserved by all potent growth hormones. All fragments generated during these studies, whether produced from natural products, or synthesized, will be screened for the ability to inhibit any of the known biochemical functions of hGH.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK018677-11
Application #
3226111
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1979-04-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
11
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143