The amino acid sequence of porcine thyrocalcitonin.

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Abstract
The covalent structure and complete amino acid sequence of porcine thyro-calcitonin has been deduced. Proof that this proposed structure is correct requires synthesis of the peptide followed by demonstration that the synthetic product has full biological and immunological activity. All 32 amino acids in the polypeptide were positioned through repetitive degradations by the Edman procedure. The phenyl-thiohydantoin [PTH] derivatives were identified by multiple criteria; high yields of the cleavage products at each step were achieved as shown both by direct analysis of the PTH-amino acids formed and by subtractive analysis of the residual peptide after degradation. A 2nd approach involved the separation and analysis of 59 peptide subfragments of the molecule produced by enzymic and limited acid hydrolysis. Analysis of these numerous peptides was in total agreement with the sequence deduced from the Edman degradations; in fact, this 2nd approach also provided a unique solution for the amino acid sequence identical to that based on the Edman procedure. This proposed sequence was completely supported by the results found after digestion of the native polypeptide and large peptide sub-fragments by exopeptidases. The thyrocalcitonin peptide has several distinctive structural features. The single tyrosine and tryptophan are adjacent; the proportion of charged amino acids is low. There is a 1-7 intrachain disulfide bridge, providing a 23-membered ring at the amino-terminus. The carboxyl-terminal amino acid is pro-linamide. The terminal disulfide loop and the alpha-carboxyl amide are analogous to structural features found in oxytocin and vasopressin. The portions of this structure important for biological and immunological activity was not yet known; however, methionine, residue 25, may be alkylated or oxidized without loss of biological activity of the thyrocalcitonin derivative.

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