Synthesis of single-stranded labelled oligonucleotides of preselected sequence

A process for chemically synthesizing a modified single-stranded oligonucleotide comprising:

• adding at a preselected position in said oligonucleotide a modified nucleotide compound having the structure:
• ##STR22## wherein B is a pyrimidine or purine base and R is a linker arm including a blocked functional group, and provided that
• when R.sub.4 is a blocking group then
• R.sub.5 is a reactive phosphorous-containing group or is a hydrogen atom if the 5'-hydroxyl group of the 5'-terminal nucleotide of a growing oligonucleotide contains a reactive phosphorous-containing group;
• and
• when R.sub.5 is a blocking group then
• R.sub.4 is a reactive phosphorous-containing group or is a hydrogen atom if the 3'-hydroxyl group of the 3'-terminal nucleotide of a growing oligonucleotide contains a reactive phosphorous-containing group;
• and
• R.sub.8 is a hydrogen atom or a blocked hydroxyl group,
• wherein said addition is carried out under conditions to effect coupling of the reactive phosphorous-containing groups of said modified nucleotide to a reactive 3'- or 5'-hydroxyl of the oligoncleotide while not impairing the reactivity of the protected reactive functionality on the linker arm R;
• and, if required, subsequently removing the blocking group from R.sub.4 or R5 and coupling one or more additional modified or unmodified nucleotide units until the synthesis of said oligonucleotide is complete.