Method of synthesizing radioisotopically labeled oligonucleotides by direct solid-phase 5' phosphitylation

Abstract

The present invention comprises a novel method of incorporating radiolabels and other type of labels at one or more predetermined sites within an oligonucleotide. In particular, the method comprises contacting a nascent, support-bound oligonucleotide having an unprotected 5' hydroxyl group with a suitable activating agent, followed by contacting the resulting activated nascent oligonucleotide with a labeled, Y-protected mononucleotide having an unprotected 3'-hydroxyl, thereby condensing the labeled mononucleotide and nascent oligonucleotide. Normal automated synthesis can then be continued to yield the oligonucleotide of desired length having the label in the desired location. This method advantageously yields oligonucleotides with high specific activity. The oligonucleotides thereby produced are useful for determining the pharmacokinetics and biodistribution of their non-radiolabeled counterparts, both in vitro and in vivo.

Dependencies are inferred from the claim text.