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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. / Thesis / Master of Science (MSc)

The isotopes ²³Na, ²⁶Mg, ⁴¹K, ⁵⁵Mn and ⁵⁹Co were activated by the use of a well collimated, ¹⁰B filtered neutron beam from a reactor. An analysis of the induced activity versus ¹⁰B filter thickness permitted studies of individual resonances of the target elements. With the assumption of a "1/E" energy dependence for the neutron flux in the beam, it was possible to obtain resonance integrals and partial widths for radiative capture for the individual resonances. The results were normalized to the resonance integral and thermal cross section of gold. Little work of this character has been done previously for these nuclides so that comparative results are not generally available. However, those values that were in the literature, did agree reasonably well with the results gotten by this author. A consistency check obtained by using the values calculated in this work to compute the thermal absorption cross sections showed that the computed cross sections were smaller than or equal to the tabulated absorption cross sections of the elements. Since additional contributions from other resonances would add on to the calculated values, the fact that the tabulated thermal cross sections were not exceeded is in the correct direction. / Ph. D.

A combination of the Galerkin procedure and the method of multiple scales is used to analyze the nonlinear forced response of circular cylindrical shells in the presence of internal (autoparametric) resonances. If ω_f and a_f denote the frequency and amplitude of a flexural mode and ω_b and a_b denote the frequency and amplitude of the breathing mode, the steady-state response exhibits a saturation phenomenon when ω_b ≈ 2w_f if the shell is excited by a harmonic load having a frequency Ω near ω_b. As the amplitude f of the excitation increases from zero, a_b increases linearly whereas a_f remains zero until a threshold is reached. This threshold is a function of the damping coefficients and ω_b -2w_f. Beyond this threshold, a_b remains constant (i.e., the breathing mode saturates) and the extra energy spills over into the flexural mode. In other words, although the breathing mode is directly excited by the load, it absorbs a small amount of the input energy (responds with a small amplitude) and passes the rest of the input energy into the flexural mode (responds with a large amplitude). / M.S.