Glycopeptide enkephalin analogs: Design, synthesis, biophysical and pharmacological evaluation of potent analgesics with reduced side-effects

Persistent Link:
http://hdl.handle.net/10150/280097
Title:
Glycopeptide enkephalin analogs: Design, synthesis, biophysical and pharmacological evaluation of potent analgesics with reduced side-effects
Author:
Palian, Michael
Issue Date:
2002
Publisher:
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 relief is one of the most fundamental, yet elusive goals of medicine. In the mammalian brain, one means of pain suppression is through activation of the opioid receptors. The opioids themselves are a broad class of centrally acting ligands that may target the delta, kappa, and/or mu opioid receptors in the brain or the spinal column in order to produce pain relief. Glycopeptides have been shown to be versatile, non-toxic alternatives to morphine-induced analgesia in mice. In order to further explore the limits of glycopeptide analgesics, we have synthesized three series of glycopeptide enkephalin analogues (linear glycopeptides, lipo-glycopeptides, and amphipathic alpha-helical glycopeptides) in order to explore the pharmacology and glycopeptide-membrane interactions associated with high-affinity receptor agonism. The three classes of compounds were designed to interact with the cellular membrane to a different degree, and in varying modes of action. Each class of compounds has presented different challenges, but display diverse in vitro and in vivo profiles. Overall, the glycopeptides have shown excellent potential as advanced drug candidates. Total synthesis, circular dichroism, 2-D NMR, molecular modeling, membrane interaction, in vitro binding, in vivo analgesia and dependence liability studies have been performed and will be discussed.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacology.; Chemistry, Organic.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Polt, Robin

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleGlycopeptide enkephalin analogs: Design, synthesis, biophysical and pharmacological evaluation of potent analgesics with reduced side-effectsen_US
dc.creatorPalian, Michaelen_US
dc.contributor.authorPalian, Michaelen_US
dc.date.issued2002en_US
dc.publisherThe University of Arizona.en_US
dc.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.en_US
dc.description.abstractPain relief is one of the most fundamental, yet elusive goals of medicine. In the mammalian brain, one means of pain suppression is through activation of the opioid receptors. The opioids themselves are a broad class of centrally acting ligands that may target the delta, kappa, and/or mu opioid receptors in the brain or the spinal column in order to produce pain relief. Glycopeptides have been shown to be versatile, non-toxic alternatives to morphine-induced analgesia in mice. In order to further explore the limits of glycopeptide analgesics, we have synthesized three series of glycopeptide enkephalin analogues (linear glycopeptides, lipo-glycopeptides, and amphipathic alpha-helical glycopeptides) in order to explore the pharmacology and glycopeptide-membrane interactions associated with high-affinity receptor agonism. The three classes of compounds were designed to interact with the cellular membrane to a different degree, and in varying modes of action. Each class of compounds has presented different challenges, but display diverse in vitro and in vivo profiles. Overall, the glycopeptides have shown excellent potential as advanced drug candidates. Total synthesis, circular dichroism, 2-D NMR, molecular modeling, membrane interaction, in vitro binding, in vivo analgesia and dependence liability studies have been performed and will be discussed.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectChemistry, Organic.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorPolt, Robinen_US
dc.identifier.proquest3060969en_US
dc.identifier.bibrecord.b43038451en_US
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