Molecular Pharmacology, Vol 5, 227-235, Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics

Specific Tritium Labeling of a Potent Gastrin Analogue

Synthesis and Pharmacological Activities of C-Terminal Gastrin Tetrapeptide Analogues

¹ Departments of Physiology and Surgery, Mount Sinai Medical and Graduate Schools of The City University of New York, New York, New York 10029 and Medical Department, Brookhaven National Laboratory, Upton, New York 11973

The synthesis of a specifically labeled C-terminal gastrin tetrapeptide analogue, tert-butoxycarbonyl-L-tryptophyl-L-norleucyl-4,5-³H-L-aspartyl-L-phenylalanine amide(compound IV), is described. This labeled peptide was obtained by catalytic tritiation of tert-butoxycarbonyl-L-tryptophyl-L-4-dehydronorleucyl-L-aspartyl-L-phenylalanine amide (II). Upon catalytic hydrogenation, the latter compound gave tert-butoxycarbonyl-L-tryptophyl-L-norleucyl-L-aspartyl-L-phenylalanine amide (III), which possessed physical properties identical with those of the authentic material. The biological properties of compounds II and III are compared with those of L-tryptophyl-L-methionyl-L-aspartyl-L-phenylalanine amide (I), the natural C-terminal tetrapeptide of gastrin, with respect to gastric secretion in the frog, rat, and dog, and pancreatic secretion in the dog.

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ACKNOWLEDGMENTS We are grateful to Dr. J. S. Morley for samples of C-terminal tetrapeptide of gastrin, for supplying us with authentic tert-butoxycarbonyl-L-tryptophyl-L-norleucyl-L-aspartyl-L-phenylalanine amide, and for access to data prior to publication. It is also a pleasure to thank Dr. M. C. Berman, for performing the amino acid analysis of the labeled tetrapeptide; Dr. William Rosenthal, for carrying out the studies on the frog mucosa; Mr. LeRoy Johnson, for giving us access to the 220-MHz NMR machine at Varian; and Miss R. Straub, for helping us during the isolation of the radioactive material.