Synthesis of a radiolabeled cyclodepsipeptide [3H-methyl]PF1022A

✍ Scribed by U. Pleiss; A. Harder; A. Turberg; M. Londershausen; K. Iinuma; N. Mencke; P. Jeschke; G. Bonse

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 404 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199601)38:1<61::aid-jlcr814>3.0.co;2-8

✦ Synopsis

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 (PFlO22-2 19). The identity of [bis-N-methyl-3H]PF1022A was determined by LC/MS. After synthesis and purification, 88.9 pg [bis-N-methyL3HIPF1022A were available showing a specific activity of 162 Ci/mmol ($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 mum. Displacement by unlabeled PF1022A was half-maximal at about 40 nM. At 1 00-fold higher concentrations the biologically much less effective optical antipodean (PF1022-001) competed for maximal 40% of the [3H]PF1022A-binding in the Ascaris srrum membrane preparation. In-vitro comparison of PF 1022A with its optical antipodean revealed a more than 100-fold higher anthelmintic activity of PF1022A against He f erakis spumosa, Nippos frongyhs brasi liensis and Trichinella spiralis.