Correlations in the Structure and Function of Human Placental Lactogen and Human Growth Hormone. I. Modification of the Disulfide Bonds

Abstract

The two disulfide bonds of human placental lactogen (hPL) and human growth hormone (hGH) were chemically modified, and the lactogenic and immunologic activities of the derivatives were compared with those of the native unmodified hormones. Reduction and alkylation with iodoacetamide and iodoacetic acid selectively disrupted the two bonds, resulting in the formation of the S—carbamidomethyl and S—carboxymethyl derivatives, respectively. Performic acid oxidation converted the half—cystine residues to cysteic acid, oxidized the methionine residues to methionine sulfone and destroyed the single tryptophan residue in each hormone. The lactogenic potency of the derivatives, as measured by the stimulation of casein synthesis in vitro in mammary gland explants, was completely retained; immunologic activity, on the other hand, was markedly decreased or abolished. Neither the tertiary structure contributed by the two disulfide bonds in each molecule nor the presence of intact methionine and tryptophan residues is essential for lactogenic activity. Therefore, the chemical features required for this effect may reside in only a portion of the polypeptide chain common to both hormones. (Endocrinology91: 721, 1972)