Radiohalogenation of oligonucleotides via trialkylstannylaryl conjugates
US5746997A · kind A · utility
Assignee
Inventor
Key dates
| Filing date | Oct 2, 1996 |
| Grant date | May 5, 1998 |
| Priority date | — |
| Expiry date | Oct 2, 2016 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K51/0491
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Halogenated oligonucleotides and particularly radiohalogenated oligonucleotides are prepared by reacting a modified oligonucleotide with a trialkylstannylaryl reagent, such as an active ester of 4-(tri-n-butyl)benzoic acid. The modified oligonucleotide has a reactive group, such as an NH.sub.2 group, covalently attached to a terminal phosphate or to a heterocyclic base, which reacts with the trialkylstannylaryl reagent to provide a trialkylstannylaryl-ODN conjugate. The trialkylstannyl group of the trialkylstannylaryl-ODN conjugate is rapidly replaced by halogen upon treatment with electrophilic halogen, such as I.sup.+, that is formed when a halogen salt is treated with an oxidizing agent. The trialkylstannylaryl-ODN conjugate is significantly more lipophilic than the halogenated ODN and is readily separated from the halogenated ODN by simple reverse phase column chromatography. The method is especially suitable to introduce radioactive iodine into ODNs and yields the first known ODN labeled with essentially isotopically pure .sup.123 I.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.