Anthrax Antigen Synthesized

CARBOHYDRATES

Anthrax, a lethal disease caused by the bacterium Bacillus anthracis, is a serious terrorism concern. In 2001, anthrax spores mailed to media and U.S. Senate offices resulted in five deaths. Antibiotics and vaccines to fight the disease are being studied by a number of research groups worldwide.

Now, researchers have achieved the first total synthesis of a key oligosaccharide from the anthrax bacteriums surface glycoprotein. Postdoc Daniel B. Werz and chemistry professor Peter H. Seeberger at the Swiss Federal Institute of Technology (ETH), Zurich, carried out the work (Angew. Chem. Int. Ed., published online Sept. 19, dx.doi.org/10.1002/anie.200502615).

The oligosaccharide includes a unique terminal sugar that has so far been found only in the anthrax bacterium. The ability to synthesize the tetrasaccharide and analogs from simple precursors could aid discovery of carbohydrate-based vaccines with selective antianthrax activity. An anthrax vaccine for humans is available, but it is hard to administer and causes some adverse reactions.

Last year, microbiology professor Charles L. Turnbough Jr. and coworkers at the University of Alabama, Birmingham, determined the structure of the anthrax bacteriums surface tetrasaccharide and discovered its unique amido-group-containing terminal sugar, which they named anthrose (J. Biol. Chem. 2004, 279, 30945).

Seeberger and coworkers prepared anthrose by a new route. They then constructed the tetrasaccharide convergently by fusing separately constructed disaccharide halves. The researchers also attached a pentenyl group that can be used to hook the tetrasaccharide or analogs to a carrier protein to potentially enhance immunogenicity.

The synthesis involves an artful finessing of differentiation between functional groups and is a nice application to a clearly important goal, says chemistry professor Samuel J. Danishefsky of Memorial Sloan-Kettering Cancer Center, New York City.