Reactivity of analogs with pancreatic tryptophan-activating enzyme

The tryptophan analogs 7-azatryptophan, tryptazan, 6-fluorotryptophan, and 5-fluorotryptophan were activated by the tryptophan-activating enzyme of pancreas in the hydroxamate test as well as for amino acid-dependent ATP-pyrophosphate exchange. Another group of analogs, including 5- and 6-methyltryptophan, is inhibitory for tryptophan activation but did not show any activation effects. A comparison of the analogs with regard to their activation by enzyme and their growth effects shows that only the enzyme-activated analogs appear to be first incorporated into protein (3) and then block growth, presumably by erroneous protein synthesis. Other analogs, such as methyltryptophan, are not enzymically activated but compete with tryptophan for enzyme activation. These appear to inhibit growth immediately and are not incorporated into protein. The parallel between analog incorporation and its activation by the amino acid-activating enzyme seems to confirm the assumption that these amino acid-activating enzymes are part of the protein-synthesizing apparatus.