Synthesis, pharmacology, and structural analysis of opioid peptides: Cyclic somatostatin analogs which include unusual amino acids with conformationally restricted side-chain groups

Persistent Link:
http://hdl.handle.net/10150/282318
Title:
Synthesis, pharmacology, and structural analysis of opioid peptides: Cyclic somatostatin analogs which include unusual amino acids with conformationally restricted side-chain groups
Author:
Bonner, Grady Gregg, 1965-
Issue Date:
1997
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:
This work relates the activities of Somatostatin-derived opioid peptides to their 3-dimensional structures. Due to the flexability of peptides, they adopt multiple conformations. This flexibility leads to ambiguity in the development of structure-activity profiles. Here flexibility is reduced by incorporation of amino acids with conformationally restricted side-chain groups. These groups are restricted to certain topographies by cyclization or biased through substitution at the beta carbon. The opioid activities of these peptides are determined by brain binding radioligand competition assay, in vitro activity in the mouse vas deferens (MVD) and guinea pig ileum (GPI) smooth muscle twitch-height inhibition assays, and in vivo in the mouse warm water tail-flick latency assay. Their 3-dimensional structures were determined through a variety of 2D 1H NMR including TOCSY, ROESY, DQF-COSY, and COSY-35, as well as molecular modeling including energy minimization and molecular dynamics. By knowing the activity of the peptides, and their preferred conformations, a reasonably confident structure-activity profile was generated.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacology.; Chemistry, Biochemistry.; Chemistry, Organic.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Biochemistry
Degree Grantor:
University of Arizona
Advisor:
Hruby, Victor J.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleSynthesis, pharmacology, and structural analysis of opioid peptides: Cyclic somatostatin analogs which include unusual amino acids with conformationally restricted side-chain groupsen_US
dc.creatorBonner, Grady Gregg, 1965-en_US
dc.contributor.authorBonner, Grady Gregg, 1965-en_US
dc.date.issued1997en_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.abstractThis work relates the activities of Somatostatin-derived opioid peptides to their 3-dimensional structures. Due to the flexability of peptides, they adopt multiple conformations. This flexibility leads to ambiguity in the development of structure-activity profiles. Here flexibility is reduced by incorporation of amino acids with conformationally restricted side-chain groups. These groups are restricted to certain topographies by cyclization or biased through substitution at the beta carbon. The opioid activities of these peptides are determined by brain binding radioligand competition assay, in vitro activity in the mouse vas deferens (MVD) and guinea pig ileum (GPI) smooth muscle twitch-height inhibition assays, and in vivo in the mouse warm water tail-flick latency assay. Their 3-dimensional structures were determined through a variety of 2D 1H NMR including TOCSY, ROESY, DQF-COSY, and COSY-35, as well as molecular modeling including energy minimization and molecular dynamics. By knowing the activity of the peptides, and their preferred conformations, a reasonably confident structure-activity profile was generated.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectChemistry, Biochemistry.en_US
dc.subjectChemistry, Organic.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineBiochemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorHruby, Victor J.en_US
dc.identifier.proquest9729478en_US
dc.identifier.bibrecord.b34802162en_US
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