FAILURE OF STREPTOZOTOCIN TETRAACETATE TO UNDERGO EXTENSIVE HYDROLYSIS AND TO INHIBIT D-GLUCOSE METABOLISM AND INSULINOTROPIC ACTION IN RATPANCREATIC-ISLETS

The esterification of several monosaccharides, such as D-glucose, D-ma nnoheptulose and 2-deoxy-D-glucose was recently reported to increase t heir biological efficiency as either nutrient or antimetabolic agent. In the present study, however, the tetraacetate ester of streptozotoci n was unexpectedly found to be less potent than unesterified streptozo tocin in inhibiting D-glucose metabolism and insulinotropic action in isolated rat pancreatic islets. This coincided with a much lower rate for the hydrolysis of streptozotocin tetraacetate than D-glucose penta acetate in islet homogenates. These findings document that the esterif ication of single sugars is not always a successful procedure to enhan ce their biological potency, for instance because of too low a rate fo r the intracellular hydrolysis of the ester. To the extent that the ac tivity of the concerned esterase(s) may differ in distinct cell types, as suggested by a prior observation, advantage could be taken of such a situation to target selected esters towards specific, e.g. tumoural cells. (C) 1998 John Wiley & Sons, Ltd.