The 69-84 amino acid region of the parathyroid hormone molecule is essential for the interaction of the hormone with the binding sites with carboxyl-terminal specificity.

We evaluated the competitive inhibitory effect of intact PTH, the amino-terminal PTH(1-34) fragment, and a series of truncated carboxyl-terminal PTH fragments on the binding of internally 35S-labeled human PTH(1-84) ([35S]hPTH(1-84)) to osteoblastic cells (ROS 17/2.8), in order to identify the minimum and critical elements within the PTH molecule for the interaction with the binding sites specific for the carboxyl-terminal region of the hormone. When the amino-terminal region of the PTH molecule was truncated stepwise, hPTH(35-84), hPTH(53-84) and hPTH(69-84), but not hPTH(70-84), significantly inhibited the [35S]hPTH(1-84) binding. On the other hand, the simple deletion of the carboxyl-terminal glutamine at position 84 of hPTH(53-84) [hPTH(53-83)] resulted in blunting the inhibitory effect of the peptide on the [35S]hPTH(1-84) binding. Furthermore, hPTH(35-84), hPTH(53-84) and hPTH(69-84), but not hPTH(70-84) nor hPTH(53-83), augmented the inhibitory effect of the amino-terminal PTH fragment [hPTH(1-34)]...