The phosphoramidite method of oligonucleotide synthesis has been invaluable. WIth a few reagents and an expensive machine, you can make any sequence of DNA or RNA. Purification can be a bit tricky, and it only gets worse as you get longer (once you're up to about 100 bases, you probably have a third or less of your desired stuff, the rest is shorter, truncated strands). That said, it's pretty amazing - making a strand of DNA or RNA is as simple as spelling it out.
Oligos are important! The polymerase chain reaction needs two of them. Companies have been set up exclusively to sell them. Can you imagine explaining to Watson and Crick that you could type a DNA sequence into a computer, pay a few bucks, and have it on your doorstep in a day?
They're only getting more important, too. Oligos play a central role in techniques like RNA interference. Another nucleic acid therapeutic technique, antisense, wasn't the magic bullet everyone was hoping for, but it has had one product make it to market. More on that in a minute.
One problem with any nucleic acid therapeutic is that your body tends to chop them up - they don't belong there, and your body has enzymes to handle foreign DNA. If we go a step down on the periodic table, however, and use a sulfur instead of an oxygen, we've got a phosphorothioate ester instead of a phosphate ester, which the enzymes don't work as well on.
Normally, DNA synthesis involves a mild oxidation step, with iodine and water - this makes the P(III) (phosphite) ester into the P(V) (phosphate) ester we know and love. Replacing the iodine step with a Beaucage's reagent step results in a sulfur-containing phosphorothioate ester instead of the oxygen-only phosphate ester. This imparts nuclease resistance into whatever oligo you're after. Fomivirsen, an antisense oligo, is all phosphorothioate linkages.
It goes like so:
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