Aptamer Chemistry : The Philosopher’s Stone

Bernard Trevisan ,an unfortunately fictional character, is attributed with spending his life in the scientific pursuit of the Philospher’s Stone, a substance that could transform a base metal into gold. Although Bernard was not ultimately successful, he represents all of those alchemists who built the basis of chemistry through the development of rigorous scientific methods.

Our use of gold with aptamers is in some ways no less mysterious though. For conjugation of aptamers to gold surfaces we routinely synthesize them with a disulphide group on either the 5’ or 3’ end. Gold has the interesting property of being able to reduce the disulphide group into thiols and then to oxidize the thiols in a strong metallic bond.

The following diagram provides the structure of the 5’ disulphide provided by IDT-DNA.

The reduction of the disulphide results in two fragments being produced. Both of these fragments (the one containing just a C6  chain, and the other with a C6 chain prior to the aptamer) will be released and both will conjugate to the gold surface. This is something to keep in mind in terms of selecting the chemical structure that you choose for any given application. We think that the presence of the second fragment is beneficial in terms of providing a spacer on the surface.

We use this chemistry routinely in our laboratory for the conjugation of aptamers to gold surfaces for surface plasmon resonance imaging, for conjugation to gold nanoparticles and we are involved with partners in several efforts to use gold as the functional surface for aptamers in biosensors.

Perhaps aptamers are the Philosopher’s Stone. They are made synthetically from base elements: carbon, nitrogen, oxygen, hydrogen, and phosphate and have the ability to heal forms of illness. Just remember that according to Theophrastus Paracelsus in The Book of the Revelation of Hermes, the Philosopher’s Stone must be diluted with wine.