We will continue our studies on the enzymology of certain peptide hormones: Angiotensin I, atrial natriuretic peptides, hypothalmic gonadotropin releasing hormone (GnRH), and GnRH associated peptide (GAP) which may be prolactin releasing inhibiting hormone.
Our aims are: 1. To determine the catalytic role of the active site glutamic acid of converting enzyme and to determine the nature of the active site. To explain substrate inhibition and noncompetitive inhibition. To study the nature of the shift in the cleavage site. 2. To sequence converting enzyme from its cDNA. 3. To purify and study atrial PDH (recently discovered in this laboratory) with respect to its role in processing the C termini of atrial natriuretic peptides. To see if it contains an active site glutamic acid. 4. To chemically sequence a very small active site peptide of atrial PDH and to sequence about 200 amino acids of the active site from cDNA. 5. To purify and study an enzyme (recently discovered in this laboratory) that processes the N terminus of atrial natriuretic peptides. 6. To purify and study GAP releasing enzyme (recently discovered in this laboratory) in relationship to its physiological role. 7. To look for enzyme(s) that process the C terminus of GnRH.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL022242-13
Application #
3336782
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1978-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
13
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Kundu, G C; Schullek, J R; Wilson, I B (1994) The alkylating properties of chlorambucil. Pharmacol Biochem Behav 49:621-4
Kundu, G C; Wilson, I B (1993) Endothelin-converting enzyme: the binding of metal ions. Int J Pept Protein Res 42:64-7
Kundu, G C; Wilson, I B (1992) Identification of endothelin converting enzyme in bovine lung membranes using a new fluorogenic substrate. Life Sci 50:965-70
Schullek, J R; Wilson, I B (1989) Purification of bovine angiotensin converting enzyme. Life Sci 45:685-90
Schullek, J R; Wilson, I B (1989) Angiotensin converting enzyme: substrate inhibition. Peptides 10:431-4
Schullek, J R; Wilson, I B (1988) The binding of zinc to angiotensin-converting enzyme. Arch Biochem Biophys 265:346-50
Palen, T E; Harris, R B; Wypij, D M et al. (1987) Substrate specificity of a hypothalamic neurosecretory granule enzyme capable of processing pro-gonadotropin releasing hormone precursor protein. Peptides 8:21-4
Deluca-Flaherty, C; Schullek, J R; Wilson, I B et al. (1987) Hybridization and partial cDNA sequence analyses of bovine lung angiotensin I-converting enzyme. Int J Pept Protein Res 29:678-84
Harris, R B (1986) Isolation and sequencing of an active-site peptide from angiotensin I-converting enzyme. Adv Exp Med Biol 198 Pt A:513-21
Palen, T E; Wypij, D M; Wilson, I B et al. (1986) Characterization of an enzyme that is capable of processing pro-gonadotropin-releasing hormone protein. Arch Biochem Biophys 251:543-50

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