The design and synthesis of imine-bridged cyclic peptides andthe solid phase synthesis of β-turn mimetics
Author
Andrus, Danice M.Issue Date
2004Keywords
Chemistry, Organic.Advisor
Hruby, Victor J.
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The University of Arizona.Rights
Copyright © 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.Abstract
Pain is perhaps the most unpleasant sensation humans experience. While pain is important in preventing further injury and as a detection mechanism for ill-health; effective relief of pain, especially chronic or neuropathic, is a critical quality of life issue. As discoveries are made regarding opioid receptor-acceptor-ligand interactions, ligands that bind specifically to a receptor subtype can modify behavior without triggering side effects. Topographical space control is an important consideration in ligand design. According to Ramachandran¹, α-amino acids are confined to the following low-energy conformations, α-helix, β-sheets, extended structures, and β-turns. Endogenous peptides such as the enkephalins and endomorphins activate the opioid receptor subtypes, δ- and μ-, respectively, and are involved in the pain cascade. Research herein concerns the synthesis of δ-opioid peptidomimetics that replace the Gly-Gly unit of Leu-enkephalins with a β-turn mimetic moiety. Additionally, using the bioactive nostocyclopeptolides as templates, smaller cyclized imino-bridged peptides were designed. These peptides were developed with the mu-opioid subtype requirements in mind.Type
textThesis-Reproduction (electronic)
Degree Name
M.S.Degree Level
mastersDegree Program
Graduate CollegeChemistry