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New page: left|200px<br /><applet load="1b0q" size="450" color="white" frame="true" align="right" spinBox="true" caption="1b0q" /> '''DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED ...
 
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[[Image:1b0q.gif|left|200px]]<br /><applet load="1b0q" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1b0q" />
'''DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION'''<br />


==Overview==
==DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION==
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.
<StructureSection load='1b0q' size='340' side='right'caption='[[1b0q]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1b0q]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B0Q FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=RE:RHENIUM'>RE</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1b0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b0q OCA], [https://pdbe.org/1b0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b0q RCSB], [https://www.ebi.ac.uk/pdbsum/1b0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b0q ProSAT]</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.


==About this Structure==
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>
1B0Q is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ] with RE, ACE and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1B0Q OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9788997 9788997]
</div>
[[Category: Protein complex]]
<div class="pdbe-citations 1b0q" style="background-color:#fffaf0;"></div>
[[Category: Giblin, M.F.]]
== References ==
[[Category: Hoffman, T.J.]]
<references/>
[[Category: Jurisson, S.S.]]
__TOC__
[[Category: Quinn, T.P.]]
</StructureSection>
[[Category: Wang, N.]]
[[Category: Large Structures]]
[[Category: ACE]]
[[Category: Giblin MF]]
[[Category: NH2]]
[[Category: Hoffman TJ]]
[[Category: RE]]
[[Category: Jurisson SS]]
[[Category: alpha melanocyte stimulating hormone]]
[[Category: Quinn TP]]
[[Category: peptide]]
[[Category: Wang N]]
[[Category: rhenium technetium]]
 
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DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION

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