1b0q: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1b0q.gif|left|200px]]< | [[Image:1b0q.gif|left|200px]] | ||
'''DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION''' | {{Structure | ||
|PDB= 1b0q |SIZE=350|CAPTION= <scene name='initialview01'>1b0q</scene> | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=RE:RHENIUM'>RE</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene> and <scene name='pdbligand=NH2:AMINO GROUP'>NH2</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1B0Q is a [ | 1B0Q is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B0Q OCA]. | ||
==Reference== | ==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:[http:// | 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://www.ncbi.nlm.nih.gov/pubmed/9788997 9788997] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Giblin, M F.]] | [[Category: Giblin, M F.]] | ||
| Line 24: | Line 33: | ||
[[Category: rhenium technetium]] | [[Category: rhenium technetium]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:04:46 2008'' | ||
Revision as of 08:04, 20 March 2008
| |||||||||||||
| 1b0q | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | RE, ACE and NH2 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
DITHIOL ALPHA MELANOTROPIN PEPTIDE CYCLIZED VIA RHENIUM METAL COORDINATION
Overview
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
1B0Q is a Protein complex structure of sequences from [1]. Full crystallographic 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 Thu Mar 20 10:04:46 2008
