Design, synthesis, conformation and biological activities of cyclic alpha-melanotropin and related compounds.
AuthorAhmed, Al-Obeidi Fahad.
AdvisorHruby, Victor J.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractThis research initiated an investigation of the structural relationships between melanocyte stimulating hormone (α-MSH) and its melanin dispersion on lizard (Anolis carolinensis) and frog (Rana pipiens) skins bioassays as representing models for mammalian and amphibian melanocytes, respectively. From previous extensive structure-activity relationships of α -MSH together with the theoretical modeling we were able to design a group of linear and cyclic peptides related to "4-10" fragment analogues of α -MSH. The solid phase synthesis of α -MSH and its related analogues using the p-methyl-benzhydrylamine resin was accomplished. The C-terminal carboxamide and N-terminal acetylamide were maintained in all peptides synthesized. The cyclic peptides were prepared in solution phase using the linear peptides generated by solid phase. All the cyclization were done by using the hydrochloride salts of the peptide and DMF as solvent with diphenylphosphoryl azide (DPPA) as a coupling reagent in the presence of K₂HPO₄ as a base. The yields of the cyclic peptides were in the range of 30-40 percent. In all the synthesized peptides the replacement of D-Phe⁷ with L-Phe⁷ causes reduction in the potency of the peptide on lizard or frog skins bioassays. Also, the reduction or increase in ring size in the cyclic peptide from a 23 membered ring diminishes the biological effect of the peptide under testing.