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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2011-3-3
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pubmed:abstractText |
By use of a solid-phase synthetic approach, a bioactive reverse turn heterocycle was incorporated into a cyclic peptide template to probe melanocortin receptor potency and ligand structural conformations. The five melanocortin receptor isoforms (MC1R-MC5R) are G-protein-coupled receptors (GPCRs) that are regulated by endogenous agonists and antagonists. This pathway is involved in pigmentation, weight, and energy homeostasis. Herein, we report novel analogues of the chimeric AGRP-melanocortin peptide template integrated with a small molecule moiety to probe the structural and functional consequences of the core His-Phe-Arg-Trp peptide domain using a reverse-turn heterocycle. A series of six compounds are reported that result in inactive to full agonists with nanomolar potency. Biophysical structural analysis [2D (1)H NMR and computer-assisted molecular modeling (CAMM)] were performed on selected analogues, resulting in the identification that these peptide-small molecule hybrids possessed increased flexibility and fewer discrete conformational families compared to the reference peptide and result in a novel template for further structure-function studies.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Agouti-Related Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Heterocyclic Compounds, 1-Ring,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Melanocortins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidomimetics,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Melanocortin,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfides
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1379-90
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pubmed:meshHeading |
pubmed-meshheading:21306168-Agouti-Related Protein,
pubmed-meshheading:21306168-Amino Acid Sequence,
pubmed-meshheading:21306168-Animals,
pubmed-meshheading:21306168-HEK293 Cells,
pubmed-meshheading:21306168-Heterocyclic Compounds, 1-Ring,
pubmed-meshheading:21306168-Humans,
pubmed-meshheading:21306168-Ligands,
pubmed-meshheading:21306168-Magnetic Resonance Spectroscopy,
pubmed-meshheading:21306168-Melanocortins,
pubmed-meshheading:21306168-Mice,
pubmed-meshheading:21306168-Models, Molecular,
pubmed-meshheading:21306168-Molecular Conformation,
pubmed-meshheading:21306168-Molecular Sequence Data,
pubmed-meshheading:21306168-Oligopeptides,
pubmed-meshheading:21306168-Peptide Fragments,
pubmed-meshheading:21306168-Peptides, Cyclic,
pubmed-meshheading:21306168-Peptidomimetics,
pubmed-meshheading:21306168-Protein Structure, Secondary,
pubmed-meshheading:21306168-Receptors, Melanocortin,
pubmed-meshheading:21306168-Stereoisomerism,
pubmed-meshheading:21306168-Structure-Activity Relationship,
pubmed-meshheading:21306168-Sulfides
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pubmed:year |
2011
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pubmed:articleTitle |
Incorporation of a bioactive reverse-turn heterocycle into a peptide template using solid-phase synthesis to probe melanocortin receptor selectivity and ligand conformations by 2D 1H NMR.
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pubmed:affiliation |
Department of Pharmacodynamics, University of Florida, Gainesville, Florida 32610, United States.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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