1b0q
From Proteopedia
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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] with RE, ACE and NH2 as ligands. 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
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