Structural basis of biological and immunological activity of parathyroid hormone.

Abstract

The amino acid composition of parathyroid hormone and its component tryptic peptides showed that the molecule was quite basic; lysine and arginine were clustered in certain areas, giving these regions a highly positive charge. The analysis of the covalent sequence is incomplete but the current information provided a useful model of the structure. A minimum structure requisite for biological activity appeared to reside in approximately 25% of the molecule, a sequence 20 amino acids long at the COOH-terminus of the polypeptide chain. A slightly smaller segment in the same region was important for immunological reactivity. Prolonged digestion of the native hormone by carboxypeptidase or selective chemical alteration of the methionine, tryptophan, or tyroslne located within the carboxy-terminal region caused marked loss of biological activity, but immunological activity was seriously impaired only by oxidizing the tyrosine. It is unlikely that the complete covalent sequence of parathyroid hormone will be available shortly; this information may allow one to correlate further the chemical structure of the hormone with its biological actions.