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http://hdl.handle.net/11375/22766
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DC Field | Value | Language |
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dc.contributor.advisor | Epand, R. M. | - |
dc.contributor.author | Lancaster, Charles | - |
dc.date.accessioned | 2018-04-27T16:09:25Z | - |
dc.date.available | 2018-04-27T16:09:25Z | - |
dc.date.issued | 1990-09 | - |
dc.identifier.uri | http://hdl.handle.net/11375/22766 | - |
dc.description.abstract | The structural requirements for the binding of dynorphin to the kappa opioid receptor are of profound clinical interest in the search for a powerful non-addictive analgesic. These requirements are thought to be met by the membrane-mediated conformation of the opioid peptide dynorphin A-(1-13}, Tyr¹-Gly²-Gly³-Phe⁴-Leu⁵-Arg⁶-Arg⁷-Ile⁸-Arg⁹-Pro¹⁰-Lys¹¹-Leu¹²-Lys¹³. Schwyzer [𝘉𝘪𝘰𝘤𝘩𝘦𝘮𝘪𝘴𝘵𝘳𝘺 25: 4281-4286 (1986)] has proposed an essentially α-helical membrane-mediated conformation of the tridecapeptide. In the present study, the hydrophobic moment, the helix probability and a four -state secondary structure prediction were computed. They signified, in agreement with circular dichroism (CD) studies on phospholipid-bound dynorphin A-(1-13)-tridecapeptide, negligible helical content of the peptide. CD studies demonstrated that the aqueous-membraneous interphase can be mimicked by methanol. The 500 and 620 MHz ¹H nuclear magnetic resonance (NMR) spectra of dynorphin A-(1-13) in methanolic solution were sequence-specifically assigned with the aid of correlated spectroscopy (COSY), double-quantum filtered phase-sensitive COSY, relayed COSY (RELAY) and nuclear Overhauser enhancement spectroscopy (NOESY). 2-D CAMELSPIN/ROESY experiments indicated that at least the part of the molecule from Arg⁷ to Arg⁹ was in an extended or β-strand conformation, which was in line with deuterium exchange and temperature dependence studies of the amide protons. ¹³C_α spin-lattice relaxation rate constants indicated a non-rigid backbone conformation. Transferred nuclear Overhauser effect studies on aqueous systems containing dynorphin A-(1-13) in the presence of dimyristoyl-phosphatidylcholine bilayers indicated a folded conformation from Tyr¹ to Leu⁵. The findings were incorporated into a tentative molecular model, which also indicated a non-helical, non-extended conformation for the rest of the molecule in the presence of corresponding distance-restrained negative charges. | en_US |
dc.language.iso | en | en_US |
dc.subject | dynorphin | en_US |
dc.subject | peptide | en_US |
dc.subject | dichroism | en_US |
dc.subject | magnetic resonance | en_US |
dc.title | The Membrane-Mediated Conformation of Dynorphin A-(1-13)-Peptide as Studied by Nuclear Magnetic Resonance Spectroscopy, Circular Dichroism Spectropolarimetry, and Molecular Dynamics | en_US |
dc.title.alternative | The Membrane-Mediated Conformation of Dynorphin A-(1-13) | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Digitized Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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lancaster_charles_r_d_1990Sept_masters.pdf | 18.91 MB | Adobe PDF | View/Open |
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