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{{Theoretical_model}}
==TRITHIOL ALPHA MELANOCYTE STIMULATING HORMONE CYCLIZED THROUGH RHENIUM COORDINATION==
<StructureSection load='2msh' size='340' side='right' caption='[[2msh]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MSH FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2msh FirstGlance], [http://www.ebi.ac.uk/pdbsum/2msh PDBsum]</span></td></tr>
<table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
alpha-Melanocyte stimulating hormone (alpha-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind alpha-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, D-Phe7-alpha-MSH4-13 analog. Structural analysis of the Re-peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate-metal-thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re-peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re-alpha-MSH analog. Characterization of the second-generation Re-peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of alpha-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties.


[[Image:2msh.png|left|200px]]
Design and characterization of alpha-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination.,Giblin MF, Wang N, Hoffman TJ, Jurisson SS, Quinn TP Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12814-8. PMID:9788997<ref>PMID:9788997</ref>


{{STRUCTURE_2msh|  PDB=2msh  |  SCENE=  }}
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
===TRITHIOL ALPHA MELANOCYTE STIMULATING HORMONE CYCLIZED THROUGH RHENIUM COORDINATION===
== References ==
 
<references/>
{{ABSTRACT_PUBMED_9788997}}
__TOC__
 
</StructureSection>
==Reference==
<ref group="xtra">PMID:009788997</ref><references group="xtra"/>
[[Category: Giblin, M F]]
[[Category: Giblin, M F]]
[[Category: Hoffman, T J]]
[[Category: Hoffman, T J]]
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