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Chemical Biology

A supplement providing a snapshot of the latest developments in chemical biology



Unnatural sugar enantiomers join fight against disease


15 February 2006

Additional pharmaceutical products could be developed thanks to researchers who have tested the enzyme inhibition activities of unnatural sugar enantiomers of two known drugs.

Keith Clinch from Industrial Research Limited, New Zealand, and colleagues have prepared the L-nucleoside analogues of two D-nucleoside pharmaceuticals currently undergoing clinical trials in order to try to find new drugs.

L-enantiomer of immucillin-H against leukemia

Immucillin-H is in Phase II trials as an anti-leukaemia agent and DADMe-Immucillin-H is in Phase I trials as an anti-psoriasis drug. The L-enantiomers of these drugs were prepared and tested as enzyme inhibitors by their ability to bind the enzyme purine nucleoside phosphorylase (PNPase). The human and bovine forms of the PNPases were tested and compared with those obtained for the original, D-nucleoside forms of the drugs.

Despite being less active than the D-enantiomer, the L-enantiomer of Immucillin-H was still potent. L-Immucillin-H was found to be more active than some analogues of D-Immucillin-H as an inhibitor of the human PNPase enzyme. L-DADMe-Immucillin-H proved to be quite potent as a sub-nanomolar inhibitor against human and bovine PNPase enzymes. Interest in these compounds has increased as they too have the potential to become pharmaceutical products.

Elinor Richards

References

K Clinch et al., Org. Biomol. Chem., 2006, (DOI: 10.1039/b517883e)