Alpha-fetoprotein derived synthetic peptides: assay of an estrogen-modifying regulatory segment.
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.
Mizejewski
G J
GJ
Wadsworth Center, Albany, NY 12201-0509, USA.
Dias
J A
JA
Hauer
C R
CR
Henrikson
K P
KP
Gierthy
J
J
D000595:Amino Acid Sequence; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000138:chemical synthesis; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000032:analysis* / Q000138:chemical synthesis
D010455:Peptides; D000509:alpha-Fetoproteins; D004958:Estradiol