Greenland, W.E.P. and Howland, K. and Hardy, J. and Fogelman, I. and Blower, P.J. (2003) Solid-phase synthesis of peptide radiopharmaceuticals using Fmoc-N-epsilon-(hynic-Boc)-lysine, a technetium-binding amino acid: application to Tc-99m-labeled salmon calcitonin. Journal of Medicinal Chemistry, 46 (9). pp. 1751-1757. ISSN 0022-2623 .
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Abstract
Labeling of proteins with metallic radionuclides for use in radiopharmaceuticals involves covalently attaching a bifunctional chelator. In principle, use of smaller peptides allows this chelator to be incorporated during solid-phase peptide synthesis (SPPS) with total site specificity. To realize the advantages of this approach, a lysine-hynic conjugate Fmoc-N-epsilon-(Hynic-Boc)-Lys was synthesized for incorporating the well-known technetium-99m-binding hydrazinonicotinamide ligand into peptides during SPPS. It was used to synthesize a technetium-99m-labeled salmon calcitonin with the hynic-linked amino acid in place of lysine-18. A trifluoroacetate group protected the hynic during alkaline oxidation to the cyclic disulfide and was readily removed by mild acid treatment. The peptide was efficiently labeled (91-98% radiochemical yield) with Tc-99m in the presence of tricine and SnCl(2) with high specific activity (>100 MBq/microg). The product showed good serum stability and specific affinity for human calcitonin receptors. Fmoc-N-epsilon-(Hynic-Boc)-Lys is a highly versatile technetium-binding amino acid for incorporation into peptides during SPPS. This allows total flexibility and control in the site of attachment and is suitable for a combinatorial approach to peptide radiopharmaceuticals.
| Item Type: | Article |
|---|---|
| Additional information: | 0022-2623 (Print) Journal Article |
| Uncontrolled keywords: | Calcitonin/*chemistry Chelating Agents/chemical synthesis/chemistry Chromatography, High Pressure Liquid Humans Hydrazines/chemistry Isotope Labeling Lysine/analogs & derivatives/*chemical synthesis/chemistry/metabolism Nicotinic Acids/*chemical synthesis/chemistry/metabolism Radiopharmaceuticals/*chemical synthesis/chemistry/metabolism Receptors, Calcitonin/metabolism Spectrometry, Mass, Electrospray Ionization *Technetium Tumor Cells, Cultured |
| Subjects: | Q Science |
| Divisions: | Faculties > Science Technology and Medical Studies > School of Biosciences |
| Depositing User: | Sue Davies |
| Date Deposited: | 10 Sep 2008 10:07 |
| Last Modified: | 12 Jun 2012 10:21 |
| Resource URI: | http://kar.kent.ac.uk/id/eprint/7163 (The current URI for this page, for reference purposes) |
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