ALPHA-FETOPROTEIN DERIVED SYNTHETIC PEPTIDES - ASSAY OF AN ESTROGEN-MODIFYING REGULATORY SEGMENT

This study describes the estrogen bioassay of a synthetic peptide fash ioned after an amino acid sequence from human alpha-fetoprotein (HAFP) . The synthetic peptide (P149), modeled after a portion of the estroge n binding pocket of rat/human AFP chimeras: was produced via F-MOC sol id phase chemistry. Bioassay of P149 in the estrogen-sensitive immatur e rodent uterus demonstrated an anti-estrogenic (40-50% inhibitory) ac tivity 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 prereq uisite for inhibitory activity. The estrogen-dependent increase in ute rine thrombin and tissue factor, as determined by an enzymatic esteras e assay, was inhibited by 30% in rat uterine cytosols. In an in vitro bioassay of estrogen-induced focus formation in MCF-7 human breast can cer cultures: focus development was inhibited by 70% following peptide exposure. The mechanism of the AFP-derived peptide inhibition of estr ogen-dependent growth remains to be determined.