The aim of these studies was to examine in detail selected post-translational modifications of the biosynthetic derivatives of pro-opiomelanocortin (31K POMC) in the rat intermediate pituitary gland, and to study effects that these modifications have on biological activity. / Partial processing of the N-terminal fragment of POMC (or 16K) resulted in three derivatives: 16K$ sb{1-49},$ 16K$ sb{50-74}$ and 16K$ sb{1-74}.$ Lys$ gamma sb3$MSH, i.e. 16K$ sb{50-74},$ was completely N-glycosylated at asparagine-65 (with 4 N-acetyl-glucosamine residues). All forms of 16K$ sb{1-74}$ contained N-linked sugars in the $ gamma$-MSH portion and most have O-linked carbohydrate structures at threonine-45 (with 2 N-acetyl-galactosamine residues). The remaining 16K$ sb{1-74}$ lacked O-linked sugars, and the 1 to 49 fragment was devoid of amino sugars. All N-terminal derivatives had the same disulfide bridge arrangement. / These N-terminal peptides had no intrinsic corticotropic activities in a dispersed rat adrenal cell bioassay, but they had synergistic effects with ACTH. Nanomolar concentrations of Lys$ gamma sb3$MSH increased the steroidogenic response induced by ACTH. The O-glycosylated form of 16K$ sb{1-74}$ had greater potentiating actions which may be due to increased resistance to degradation. These findings suggest that the extent of O-glycosylation in the N-terminal fragment may direct proteolytic processing and enhance its biological activity.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.70352 |
| Date | January 1986 |
| Creators | Seger, Monica Anne. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000400326, proquestno: AAINN75875, Theses scanned by UMI/ProQuest. |
Page generated in 0.0167 seconds