Molecular Pharmacology, Vol 13, 1105-1110, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Incorporation of 2-Fluoro-L-histidine into Cellular Protein

¹ Neuroendocrinology Unit, Behavioral Biology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20014
² Section on Biochemical Mechanisms, Laboratory of Chemistry, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014
³ Laboratory of Nutrition and Endocrinology, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014

The purpose of this study was to determine whether mammalian cells can utilize 2-fluoro-L-histidine in protein synthesis. Rat pineal glands were incubated in organ culture in medium containing 2-fluoro-L-[4-³]histidine (3 mM); trichloracetic acid-insoluble material from these glands contained radioactivity. Incorporation of radioactivity was decreased in the presence of histidine (3 mM). After the ³H-labeled macromolecules were treated with a protease, over 75% of the radioactivity was soluble in trichloracetic acid. Amino acid analysis of the trichloracetic acid-soluble material indicated that the majority of the liberated radioactivity was 2-fluoro-L-[³H]histidine. These findings demonstrate that mammalian cells can incorporate 2-fluoro-L-histidine into newly synthesized proteins. In view of this, it would appear likely that the reported inhibitory effects of 2-fluoro-L-histidine on enzyme induction could result, in part, from the incorporation of the analogue into proteins.