Design and Synthesis of Neurologically Active Glycopeptides for Neuroprotection and Antinociception

Persistent Link:
http://hdl.handle.net/10150/594654
Title:
Design and Synthesis of Neurologically Active Glycopeptides for Neuroprotection and Antinociception
Author:
Jones, Evan Matthew
Issue Date:
2015
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.
Embargo:
Release 01-Nov-2016
Abstract:
Endogenous peptides modulate a wide range of physiological conditions in the central and peripheral nervous systems, but have not been harnessed to perform similar functions in pharmaceutical roles due to their ease of degradation and difficulty in introducing into the neurovascular unit. We report herein advances that evidence the wide applicability that glycosylation provides as a pathway for improving the drug-like properties of peptides. This is demonstrated by utilizing novel sugar-amino acids to modify the potent mu opioid receptor agonist DAMGO to provide antinociception, and serine glycosides to modify secretin family peptides for neuroprotection and angiotensin-(1-7) to both reduce cognitive impedance following myocardial infarction and as a treatment for peripheral neuropathy. Evidence is presented via a series of in vitro and in vivo models and assays, and demonstrates the advantageous effects of glycosylation through increased persistence in serum, greatly improved blood-brain barrier penetration, and the tolerance of receptor interactions to the addition of a carbohydrate.
Type:
text; Electronic Dissertation
Keywords:
BBB; glycopeptide; neuroprotection; PACAP; VIP; Chemistry; angiotensin
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Polt, Robin L.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleDesign and Synthesis of Neurologically Active Glycopeptides for Neuroprotection and Antinociceptionen_US
dc.creatorJones, Evan Matthewen
dc.contributor.authorJones, Evan Matthewen
dc.date.issued2015en
dc.publisherThe University of Arizona.en
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
dc.description.releaseRelease 01-Nov-2016en
dc.description.abstractEndogenous peptides modulate a wide range of physiological conditions in the central and peripheral nervous systems, but have not been harnessed to perform similar functions in pharmaceutical roles due to their ease of degradation and difficulty in introducing into the neurovascular unit. We report herein advances that evidence the wide applicability that glycosylation provides as a pathway for improving the drug-like properties of peptides. This is demonstrated by utilizing novel sugar-amino acids to modify the potent mu opioid receptor agonist DAMGO to provide antinociception, and serine glycosides to modify secretin family peptides for neuroprotection and angiotensin-(1-7) to both reduce cognitive impedance following myocardial infarction and as a treatment for peripheral neuropathy. Evidence is presented via a series of in vitro and in vivo models and assays, and demonstrates the advantageous effects of glycosylation through increased persistence in serum, greatly improved blood-brain barrier penetration, and the tolerance of receptor interactions to the addition of a carbohydrate.en
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectBBBen
dc.subjectglycopeptideen
dc.subjectneuroprotectionen
dc.subjectPACAPen
dc.subjectVIPen
dc.subjectChemistryen
dc.subjectangiotensinen
thesis.degree.namePh.D.en
thesis.degree.leveldoctoralen
thesis.degree.disciplineGraduate Collegeen
thesis.degree.disciplineChemistryen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorPolt, Robin L.en
dc.contributor.committeememberPolt, Robin L.en
dc.contributor.committeememberHruby, Victor J.en
dc.contributor.committeememberMash, Eugene A.en
dc.contributor.committeememberPemberton, Jeanne E.en
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