ORGN 598 |
| DOTA (1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid) can be chelated to metal ions to create molecular imaging probes (MIPs) for MRI, SPECT, and fluorescence imaging. Previous synthetic methods have been limited to coupling DOTA to N-terminus or side chains of peptide. To facilitate the synthesis of new peptide-based MIPs, we've developed new synthetic pathways using solution-phase/solid-phase synthesis to incorporate DOTA at C-terminus/middle of the peptide. Specifically, we've introduced an α-amino group to a side arm of DOTA, and then α-amino-DOTA-tBu was coupled to the C-terminus of peptide (PLGMWSG) in solution-phase. CBZ-α-amino-tBu-DOTA pre-loaded polymeric support was applied to DEVD-α-amino-DOTA synthesis. Also, CBZ-α-amino-tBu-DOTA was coupled to a Gly-pre-loaded polymeric support, and synthesized DEVD-α-amino-DOTA-Gly, to demonstrate that DOTA may be incorporated at any position within the backbone. Each peptide-α-amino-DOTA/Tm3+ complexes was evaluated as peptide-based MIPs by PARAmagnetic-Chemical-Exchange-Saturation-Transfer (PARACEST). Our results demonstrate that individual peptidyl MIPs and/or libraries of MIPs can be conveniently produced for molecular imaging applications. |
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New Reactions and Methodology, Heterocycles and Aromatics, Bioorganic Chemistry
8:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster
Sci-Mix
Division of Organic Chemistry |