Researchers from Slovenia have used NMR spectroscopy to home in on the ATP-binding site of the bacterial enzyme DNA gyrase. They say they now understand more clearly the nature of the interaction of this active site with EGCG, an extract of green tea thought to endow the drink with its health benefits, including antibacterial activity.

Claims for the health benefits of green, unfermented, tea ( Camellia sinensis) have been made for centuries, and are particularly apparent in Asian cultures. An ancient Chinese proverb says: "Better to be deprived of food for three days, than tea for one". Tea perhaps evolved as a way to ensure a pure disease-free water supply. The boiling process killing pathogens and the congeners provide colour and flavour.

Among those congeners are the catechins, a group of polyphenolic plant metabolites. A single cup of green tea can contain up to 200 milligrams of catechins. The biological activity of these compounds has been attributed primarily to their antioxidant properties until recently. However, green tea extract has been used in oral hygiene for centuries and suggests that green tea may have antibacterial activity too.

Now, Roman Jerala and colleagues at the National institute of Chemistry in Ljubljana, Slovenia, have homed in on this antibacterial potential and looked closely at the properties of the major catechin found in green tea, EGCG, epigallocatechin gallate.

He and his colleagues found that green tea catechins can inhibit DNA gyrase, a common target for several current antibiotics. Moreover, they utilised fluorescence spectroscopy and heteronuclear two-dimensional NMR spectroscopy (for confirmation) of the EGCG-¹⁵N-labelled gyrase B fragment complex to reveal that specific binding of EGCG takes place at the N-terminal 24 kDa fragment of gyrase B.

Compounds that target this site in particular have been sought keenly by pharmaceutical companies as potential new antibiotics, but side effects in such compounds have precluded their development to clinical practice. "We hope to avoid the problem of toxicity using compounds based on green tea catechins," Jerala explains, "which have a safety record established over centuries of tea drinking." The findings should allow researchers to design novel analogues of EGCG that improve on its activity without prohibitive side effect emerging.

"I think that this direction is worth pursuing," Jerala told SpectroscopyNOW.com, "EGCG besides being unpatentable is not vary stable in the body and has low bioavailability but this could be improved." In their paper the researchers discuss several possible research directions, however Jerala concedes that he and his colleagues lack the synthetic capabilities to pursue them. "We could only go in this direction with support from other labs," he says, "Hopefully pharmaceutical companies will consider it."

Related links:

• Med Chem, 2007, in press
• National Institute of Chemistry, Ljubljana, Slovenia

Article by David Bradley