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

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    Author
    Nyberg, Joel Benjamin
    Issue Date
    2013
    Keywords
    Melancortins
    Melanocortin 3
    Melanocortin 3 selective ligands
    Peptides
    Chemistry
    C-terminal modification
    Advisor
    Hruby, Victor J.
    
    Metadata
    Show full item record
    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
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Chemistry
    Degree Grantor
    University of Arizona
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