The NH2-terminal amino acid sequence of human proparathyroid hormone by radioisotope microanalysis

Abstract The amino terminal amino acid sequence of human proparathyroid hormone was determined by a highly sensitive radioisotope method. Fresh human parathyroid glands were incubated with one of several 3 H-labeled amino acids after which human proparathyroid hormone labeled with [ 3 H]lysine, [ 3 H]serine, [ 3 H]valine, [ 3 H]arginine, or [ 3 H]leucine was isolated. These specimens were subjected to several cycles of Edman degradation. An increase in the amount of radioactivity liberated at any cycle was taken as evidence that the amino acid at that cycle was the one with which the sample was labeled. By this approach, we found that the amino-terminal sequence of human proparathyroid hormone is lys 1 -ser 2 -val 3 -lys 4 -lys 5 -arg 6 -ser 7 -val 8 -ser 9 … leu 13 … leu 17 … lys 19 … Based on these results, we conclude that the amino-terminal region of human proparathyroid hormone consists of a hexapeptide lys-ser-val-lys-lys-arg followed by the amino acid sequence of human parathyroid hormone.