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Supramolecular! Warwick Chemists make key DNA breakthrough

Alison Rodger and Michael Hannon in their lab
Alison Rodger and Michael Hannon in their lab
Originally published 13 May 2002

Warwick researchers Dr Mike Hannon and Dr Alison Rodger, of the Department of Chemistry, have a found a class of synthetic molecules that could quite literally act as a key, locking away sections of DNA into a closely wound coil preventing proteins from interacting with particular sections of DNA code. By locking up the DNA in this way scientists could stop particular sequences of DNA from activating biological changes that doctors or scientists would rather avoid, or wish to regulate closely.

Researchers trying to devise synthetic molecules that would bind to DNA have typically only been able to produce small molecules that prefer to bind to the smaller, or minor, groove in the structure of DNA. These small molecules have also only really been able to stretch across a couple of DNA base pairs.

But now, the Warwick chemists have produced a large synthetic molecule, a Supramolecular Cylinder, which binds to the major groove of DNA, rather than the minor one, and with surprising results. When it binds to the major DNA groove the new synthetic molecule bends the particular section of DNA it is attached to. The DNA become tightly coiled together in a manner resembling the way non synthetic molecules package DNA together into chromosomes.

The ability of this synthetic molecule to coil up DNA could be used to lock up sequences of DNA so that they do not link with proteins to signal particular biological changes, thus giving scientists new tools to use in gene regulation. The strong binding mechanism to the major groove could also be used to enhance treatments that use drugs that act on DNA as such drugs must be delivered not only into the correct cell but into the nucleus as well.

The next task for the researchers will be to increase the sensitivity of the synthetic molecule to ensure that it can be used to bind to very specific DNA sequences and thus be used as a more precise tool.