Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Thesis (M.S.)--Florida State University, 2003. / Advisor: Dr. Timothy A. Cross, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed Mar. 4, 2004). Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 1988.

Thesis (Ph. D.)--University of Hong Kong, 1988.

Thesis (Ph. D.)--Worcester Polytechnic Institute. / Keywords: diffusion; tendon; NMR; fMRI. Includes bibliographical references (p. 172-179).

Thesis (Ph. D.)--Mississippi State University. Department of Chemistry. / Title from title screen. Includes bibliographical references.

Not available / text

Not available / text

Not available / text

α-MSH (α-melanotropin) is a naturally occurring linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂) that is primarily known for its ability to stimulate integumental melanocytes and more recently has been implicated in a variety of physiological and neurological processes. It has been shown that substitution of D-phenylalanine in the seven position of this hormone led to an analogue with increased potency and prolonged biological activity. Furthermore, cyclization between the four and ten positions via a cystine bridge led to analogues with enhanced potency. In this regard, a series of conformationally restricted linear and cyclic fragment analogues of α-MSH have been prepared and carefully analyzed by both biological and biophysical methods. Conformational restriction was incorporated in α-MSH fragment analogues, by: (1) substitution of sterically restricted amino acids into the native sequence; or (2) cyclization of the peptide via a disulfide bridge. Due to the biological differences observed for these synthetic α-MSH fragment analogues, a complete conformational analysis by both proton and carbon-13 NMR was performed. The conformational preferences of the backbone were examined by analyzing: (1) the alpha proton chemical shifts; (2) the amide proton chemical shifts; (3) the amide proton coupling constants; and (4) the amide proton temperature dependencies. The data suggests that the peptide backbone in both linear and cyclic analogues possesses a great amount of conformational flexibility with no hydrogen-bonded stabilization. The three-dimensional orientations of individual amino acid side chains have been examined by analyzing: (1) the chemical shifts of the side chain protons; (2) the alpha-beta coupling constants (corresponding rotamer populations); and (3) the carbon-13 spin lattice relaxation times (T₁). A careful examination a the chemical shifts of the side chains of individual amino acids in linear α-MSH fragments reveals that incorporation of an aromatic D-amino acid in the seven position results in an interaction of the side chains of the six, seven and eight positions. In addition, the low carbon-13 spin-lattice relaxation times for the β-carbons of the 5-9 sequence for both Ac-[Nle⁴]-α-MSH₄₋₁₁-NH₂ and Ac-[Nle⁴, D-Phe⁷]-α-MSH₄₋₁₁-NH₂, provides further evidence for an interaction of these side chains. Similar shielding patterns have been observed for the cyclic α-MSH fragment analogues depending upon whether L- or D-phenylalanine is incorporated in the seven position. Considering the differences in biological potency and the similarities in the NMR parameters between the linear and cyclic homologs, it can be concluded that the conformational properties that determine biological potency are too subtle to be measured by present NMR methodology. Furthermore, the similarity of the NMR shielding patterns suggests that a 23-membered ring is too large to impart significant conformational constraints on the peptide backbone or amino acid side chains.