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Further Studies on the Activity of Hadacidin^*

( Merck Institute for Therapeutic Research, Rahway, New Jersey)

Hadacidin, which was previously found to inhibit the biosynthesis de novo of adenylic acid, was also found to inhibit the formation of uridylic acid. However, the concentration of hadacidin required to partially suppress pyrimidine synthesis was much greater than that necessary to inhibit purine formation. Hadacidin did not directly inhibit the incorporation of glycine, L-leucine, and formate into proteins.

The effect of hadacidin when used with other known antitumor agents on the growth of Escherichia coli B was also investigated. The results indicated that hadacidin potentiated the growth-inhibitory activity of 2,6-diaminopurine and acted additively with 5-fluorouracil, aminopterin, amethopterin, psicofuranine, puromycin, and azaserine. Hadacidin antagonized the growth-inhibitory properties of 6-mercaptopurine and 6-azauracil.

^* This investigation was supported by the Cancer Chemotherapy National Service Center, National Cancer Institute, under the National Institutes of Health Contract Number SA-43-ph-1886.

Received 7/23/62.