The endothelins were discovered in 1988 and are known to be the most active pressor molecules in the mammalian vascular system. Endothelin-1, which shows potent and long-lasting vasoconstricting activity has been isolated from the culture medium of porcine aortic endothelial cells and implicated in a novel cardiovascular control system. The first member of endothelin family, Endothelin-1, is a 21 amino acid peptide whose structure is constrained by two disulphide bridges between residues 1-15 and 3-11. Increasing evidence for the involvement of endothelins in human disease has prompted a major effort in drug design, pharmacological evolution and structure elucidation. In this thesis, the three dimensional solution structures of Endothelin-1 and modified linear Endothelin-1 derivatives are presented using one- and two-dimensional NMR methods followed by structure calculations DIANA, DSA and MD. This is the first report of solution structures of modified linear Endothelin-1 derivatives. The Panax family plants (<I>P.ginseng</I> and <I>P.notoginseng</I>) are well known in traditional Chinese medicine with the popular name "ginseng". Major compounds isolated from the Panax family plans are saponins and the most of the saponins are also biologically active. The last chapter of this thesis presents the elucidation by one- and two-dimensional NMR methods of the structure and steriochemistry of a compound isolated from the roots of <I>Panax notoginseng</I> shown to release tissue plasminogen activator (tPA) from hemi-pituitary glands <I>in vitro</I>. The compound was identified as the saponin, ginsenoside-Rd, and its NMR spectra fully assigned for the first time.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:652400 |
| Date | January 1995 |
| Creators | Hewage, Chandralal M. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15019 |
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