Developing Melanocortin 3 Selective Ligands through C-Terminal Modification of Melanocortin Peptides

Persistent Link:
http://hdl.handle.net/10150/283606
Title:
Developing Melanocortin 3 Selective Ligands through C-Terminal Modification of Melanocortin Peptides
Author:
Nyberg, Joel Benjamin
Issue Date:
2013
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 after 13-Sep-2013
Abstract:
The melanocortin 3 and 4 receptors share 58% overall amino acid identity and 76% similarity. This high level of similarity between the MC3R and the MC4R underscores the difficulties associated with developing MC3R selective ligands, and as a consequence little is known of the physiological functions of the melanocortin 3 receptor. Previous research showing the differences between endogenous non-selective ligands and melanocortin 3 receptor selective ligands are mainly within the C-terminus of the melanocortin peptide. These findings have been exploited in this research using known melanocortin 3 and 4 selective ligands modified at their respective C-termini to develop some very promising melancortin 3 selective antagonists and agonists, analog 5 ([CO(CH₂)₂CO-DNal(2')-Arg-Trp-Lys]-Gly-Lys-Pro-Val-NH₂) and analog 20 ((H-DNal(2')-c[Asp-Pr6-DPhe-Arg-Trp-Lys]-Ala-Gly-Pro-Val-NH₂) respectively. Additional studies using molecular modeling have produced further insights into the structural basis for selectivity. Finally, we have been developing a new scaffold for the melanocortin receptor using cyclic dipeptide derivatives.
Type:
text; Electronic Dissertation
Keywords:
Melancortins; Melanocortin 3; Melanocortin 3 selective ligands; Peptides; Chemistry; C-terminal modification
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Hruby, Victor J.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleDeveloping Melanocortin 3 Selective Ligands through C-Terminal Modification of Melanocortin Peptidesen_US
dc.creatorNyberg, Joel Benjaminen_US
dc.contributor.authorNyberg, Joel Benjaminen_US
dc.date.issued2013-
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.releaseRelease after 13-Sep-2013en_US
dc.description.abstractThe melanocortin 3 and 4 receptors share 58% overall amino acid identity and 76% similarity. This high level of similarity between the MC3R and the MC4R underscores the difficulties associated with developing MC3R selective ligands, and as a consequence little is known of the physiological functions of the melanocortin 3 receptor. Previous research showing the differences between endogenous non-selective ligands and melanocortin 3 receptor selective ligands are mainly within the C-terminus of the melanocortin peptide. These findings have been exploited in this research using known melanocortin 3 and 4 selective ligands modified at their respective C-termini to develop some very promising melancortin 3 selective antagonists and agonists, analog 5 ([CO(CH₂)₂CO-DNal(2')-Arg-Trp-Lys]-Gly-Lys-Pro-Val-NH₂) and analog 20 ((H-DNal(2')-c[Asp-Pr6-DPhe-Arg-Trp-Lys]-Ala-Gly-Pro-Val-NH₂) respectively. Additional studies using molecular modeling have produced further insights into the structural basis for selectivity. Finally, we have been developing a new scaffold for the melanocortin receptor using cyclic dipeptide derivatives.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectMelancortinsen_US
dc.subjectMelanocortin 3en_US
dc.subjectMelanocortin 3 selective ligandsen_US
dc.subjectPeptidesen_US
dc.subjectChemistryen_US
dc.subjectC-terminal modificationen_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.advisorHruby, Victor J.en_US
dc.contributor.committeememberGhosh, Indraneelen_US
dc.contributor.committeememberJewett, Johnen_US
dc.contributor.committeememberMash, Eugeneen_US
dc.contributor.committeememberBrown, Michaelen_US
dc.contributor.committeememberHruby, Victor J.en_US
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