US scientists have developed a new technique for investigating the biologically active forms of the anticancer drug Taxol.

David Grant at the University of Utah, Salt Lake City, and co-workers have used novel solid state NMR techniques to establish the structure of a unique conformation of paclitaxel - more commonly known as Taxol.

Although it has been nearly 40 years since paclitaxel was discovered, little is known about the conformation of the bioactive form. 'Taxol has proven nearly impossible to structurally characterise due to its large size and flexibility,' explained Grant. 'There are many shapes it might assume.'

Structural diversity in crystals is known as polymorphism, and is a common problem with pharmaceutical and natural products. Grant's technique offers new opportunities for determining polymorph structures from crystals too small to be of use for conventional X-ray techniques.

The scientists used the solid state NMR technique to study microcrystals of paclitaxel, giving a list of experimental chemical shift tensors - values that relate NMR chemical shifts to the molecular orientation. The team then compared the tensors with computationally predicted chemical shifts for all of the possible shapes of the drug molecule to establish paclitaxel's structure.

'The development of new solid state NMR and computational methods have allowed access to a previously intractable problem,' said Grant. These techniques also open the door to deducing the structures of other polymorphic drugs. 

Jon Silversides