The Regulation of a Post-Translational Peptide Acetyltransferase: Strategies for Selectively Modifying the Biological Activity of Neural and Endocrine Peptides
Abstract
The objective of this research is to develop new strategies for pharmacologically modifying the function of peptidergic neural and endocrine cells. The results demonstrate that chemical agents which interact with cell surface receptors in the intermediate pituitary produce distinct changes in the molecular forms and, hence, the biological activity of Beta-endorphin by selectively regulating the enzymes which post-translationally process the peptide. Beta-endorphin processing in brain is also regulated through receptor activation although, in general, it appears to be more resistant to this strategy, emphasizing the need to develop agents which control peptide processing through direct enzyme inhibition or activation. Toward this goal, experiments were initiated to isolate and characterize peptide acetyltransferase, the enzyme which N-acetylates Beta-endorphin and, thereby, inactivates its opiate potency. these findings emphasize the critical importance of processing enzymes in regulating peptide biosynthesis and establish the feasibility of utilizing chemical agents targeted on these enzymes to control the function of peptidergic systems. Keywords: Acetylation; Pro- opiomelanocortin; Dopamine.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 1988
- Accession Number
- ADA202546
Entities
People
- William R. Millington
Organizations
- Uniformed Services University of the Health Sciences