Bioactive peptides, which function as hormones, neurotransmitters and neuromodulators, and are thus vitally involved in virtually all cellular functions, are known to be generated from larger precursors via a variety of postranslational modifications. In particular, carboxyl terminus amidation is a key structural feature in the bioligical activity of many bioactive peptides. It is now clear that carboxyl-terminal amidation entails two sequential enzymtic steps. The first enzyme peptidylglycine a-amidating monoxygenase (PAM) catalyzes formation of the a-hydroxyglycine derivative of the glycine extended precursor. The second enzyme, peptidylamidoglycolate lyase (PGL) ---first reported by our laboratory--catalyzes dealdylation of the a- hydroxyglycine derevatives to produce the final amidated product plus glyoxylte. Our research program focuses on this carboxly-terminal amidation inhibitors, inactvator and substrate analogs and to delineate the role amidative processing in various cellular-level processes such as vascular function and tumor cell growth.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040540-07
Application #
2900696
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Kitt, Cheryl A
Project Start
1992-02-01
Project End
2002-03-31
Budget Start
1999-04-01
Budget End
2002-03-31
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Georgia Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
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