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| | {{STRUCTURE_1b0q| PDB=1b0q | SCENE= }} | | {{STRUCTURE_1b0q| PDB=1b0q | SCENE= }} |
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| - | '''DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION'''
| + | ===DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9788997}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9788997 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9788997}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B0Q OCA]. | + | Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B0Q OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Peptide]] | | [[Category: Peptide]] |
| | [[Category: Rhenium technetium]] | | [[Category: Rhenium technetium]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:55:37 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 17:59:53 2008'' |
Revision as of 14:59, 30 June 2008
Template:STRUCTURE 1b0q
DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION
Template:ABSTRACT PUBMED 9788997
About this Structure
Full experimental information is available from OCA.
Reference
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
Page seeded by OCA on Mon Jun 30 17:59:53 2008
