Synthesis of a radiolabeled cyclodepsipeptide [3H-methyl]PF1022A
| Autor: | Andreas Turberg, Peter Jeschke, Gerhard Bonse, M. Londershausen, K. Iinuma, Achim Dipl Biol Dr Harder, Norbert Mencke, Ulrich Pleiss |
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| Rok vydání: | 1996 |
| Předmět: |
Chromatography
biology Chemistry Stereochemistry Organic Chemistry Biological activity biology.organism_classification Biochemistry Chemical synthesis Analytical Chemistry Mechanism of action Drug Discovery medicine Radiology Nuclear Medicine and imaging Specific activity Tritium Nippostrongylus brasiliensis Anthelmintic medicine.symptom Ascaris suum Spectroscopy medicine.drug |
| Zdroj: | Journal of Labelled Compounds and Radiopharmaceuticals. 38:61-69 |
| ISSN: | 0362-4803 |
| Popis: | For receptor binding studies and the elucidation of the mode of action of the potent anthelmintic compound PF1022A a tritium labeled compound with very high specific activity was necessary. Tritium was introduced into the compound by methylation of the [bis-N-demethyl]precursor of PF1022A (PF1022-219). The identity of [bis-N-methyl- 3 H]PF1022A was determined by LC/MS. After synthesis and purification, 88.9 μg [bis-N-methyl- 3 H]PF1022A were available showing a specific activity of 162 Ci/mmol (5,99 TBq/mmol) determined by mass spectrometry. The total activity was 15 mCi (555 MBq). Radiolabeled PF1022A showed an efficient and specific binding to a membrane fraction from Ascaris suum. Displacement by unlabeled PF1022A was half-maximal at about 40 nM. At 100-fold higher concentrations the biologically much less effective optical antipodean (PF1022-001) competed for maximal 40% of the [ 3 H]PF1022A-binding in the Ascaris suum membrane preparation. In-vitro comparison of PF1022A with its optical antipodean revealed a more than 100-fold higher anthelmintic activity of PF1022A against Heterakis spumova, Nippostrongylus brasiliensis and Trichinella spiralis. |
| Databáze: | OpenAIRE |
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