Alpha-fetoprotein derived synthetic peptides: assay of an estrogen-modifying regulatory segment

Abstract

This study describes the estrogen bioassay of a synthetic peptide fashioned after an amino acid sequence from human alpha-fetoprotein (HAFP). The synthetic peptide (P149), modeled after a portion of the estrogen binding pocket of rat/human AFP chimeras, was produced via F-MOC solid phase chemistry. Bioassay of P149 in the estrogen-sensitive immature rodent uterus demonstrated an anti-estrogenic (40–50% inhibitory) activity in the 23 h but not the 3–4 h uterine response. In contrast to purified HAFP, incubation of the peptide with estrogen was not a prerequisite for inhibitory activity. The estrogen-dependent increase in uterine thrombin and tissue factor, as determined by an enzymatic esterase assay, was inhibited by 30% in rat uterine cytosols. In an in vitro bioassay of estrogen-induced focus formation in MCF-7 human breast cancer cultures, focus development was inhibited by 70% following peptide exposure. The mechanism of the AFP-derived peptide inhibition of estrogen-dependent growth remains to be determined.