Molecular Pharmacology, Vol 4, 20-24, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

Structural Requirements for the Inhibition of Uridine-Deoxyuridine Phosphorylase by Thymine Nucleosides Containing an Unnatural Carbohydrate Moiety

¹ Institute of Biochemistry, German Academy of Sciences Berlin, Berlin-Buch, Germany (G. D. R.)

1-(2'-Deoxy--D-xylopyranosyl) thymine (-II) produces as great an inhibitory effect on uridine-deoxyuridine phosphorylase as 1-(2'-deoxy--D-glucopyranosyl)thymine (-I), whereas the inhibitory action of 1-(2'-deoxy--D-xylofuranosyl)thymine (V) is only 1/25 that of the above-mentioned -nucleosides. The inhibitory activity of 1-(2'-deoxy--D-xylopyranosyl) thymine (-II) is equal to that of 1-(2'-deoxy--D-glucopyranosyl)thymine (-I), both being less effective than the corresponding -anomers and more active than V. - and -1-(2'-Deoxy-D-ribopyranosyl)thymine (-III and -III) are noninhibitory under the same conditions. Hence, both the presence of a pyranose lactol ring and the xylo configuration of time hydroxyl group C-3' are necessary for the inhibitory action of these compounds. 1-(Tetrahydro-2'-pyranyl)thymine (VI) is not active.

Note:
ACKNOWLEDGMENTS We are grateful to Professor Charles Heidelberger, McArdle Laboratory for Cancer Research, University of Wisconsin, for his valuable advice in the preparation of this manuscript. The skillful technical assistance of Miss R. Wohlfeil is acknowledged.