A Novel Prosthetic Group for Site-Selective Labeling of Peptides for Positron Emission Tomography
| Autor: | Joseph Arukwe, Alan Cuthbertson, Hege Karlsen, Magne Solbakken, Ole Kristian Hjelstuen, Dag Erlend Olberg |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Fluorine Radioisotopes
Time Factors Pet chemistry Biomedical Engineering Analytical chemistry Pharmaceutical Science Bioengineering Peptide Acetates Buffers Hydroxylamines Cofactor Substrate Specificity Maleimides medicine Site selective Pharmacology chemistry.chemical_classification Binding Sites Radiochemistry Staining and Labeling medicine.diagnostic_test biology Chemistry Organic Chemistry Chemoselective ligation Temperature Hydrogen-Ion Concentration Combinatorial chemistry Positron emission tomography Positron-Emission Tomography Yield (chemistry) biology.protein Substrate specificity Peptides Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 19:1301-1308 |
| ISSN: | 1520-4812 1043-1802 |
| Popis: | Efficient methodologies for the radiolabeling of peptides with [(18)F]fluoride are a prerequisite to enabling commercialization of peptide-containing radiotracers for positron emission tomography (PET) imaging. It was the purpose of this study to investigate a novel chemoselective ligation reaction comprising conjugation of an [(18)F]-N-methylaminooxy-containing prosthetic group to a functionalized peptide. Twelve derivatives of general formula R1-CO-NH-Lys-Gly-Phe-Gly-Lys-OH were synthesized where R1 was selected from a short list of moieties anticipated to be reactive toward the N-methylaminooxy group. Conjugation reactions were initially carried out with nonradioactive precursors to assess, in a qualitative manner, their general suitability for PET chemistry with only the most promising pairings progressing to full radiochemical assessment. Best results were obtained for the ligation of O-[2-(2-[(18)F]fluoroethoxy)ethyl]-N-methyl-N-hydroxylamine 18 to the maleimidopropionyl-Lys-Gly-Phe-Gly-Lys-OH precursor 10 in acetate buffer (pH 5) after 1 h at 70 degrees C. The non-decay-corrected isolated yield was calculated to be 8.5%. The most encouraging result was observed with the combination 18 and 4-(2-nitrovinyl)benzoyl-Lys-Gly-Phe-Gly-Lys-OH, 9, where the conjugation reaction proceeded rapidly to completion at 30 degrees C after only 5 min. The corresponding non-decay-corrected radiochemical yield for the isolated (18)F-labeled product 27 was 12%. The preliminary results from this study demonstrate the considerable potential of this novel strategy for the radiolabeling of peptides. |
| Databáze: | OpenAIRE |
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