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

Greenland, William E. P. and Howland, Kevin and Hardy, Judith and Fogelman, Ignac and Blower, Philip 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 . (The full text of this publication is not available from this repository)

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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: 22 May 2014 14:28
Resource URI: http://kar.kent.ac.uk/id/eprint/7163 (The current URI for this page, for reference purposes)
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