Studies on analogs of a peptide derived from alpha-fetoprotein having antigrowth properties

A 34-amino acid portion of the third domain of alphafetoprotein possesses a ntigrowth and anticancer activities. Three analogs of this sequence were ch emically synthesized, in which the two cysteines of the original sequence w ere replaced by alanines, glycines or serines. The original cysteine and al anine peptides formed trimers at 0.20 g/L in pH 7.4 phosphate buffer, and t he glycine and serine peptides formed dimers. Trimer preparations were more potent in inhibiting estrogen-induced growth in the mouse uterine assays t han the two dimeric oligomers. Of salient importance is that the alanine pe ptide retained its trimeric form in solution much longer than the cysteine peptide. Antigrowth assays were performed starting with stock solutions at a peptide concentration of 0.20 g/L, because at very high peptide concentra tion (8.0 g/L) the peptides aggregated extensively. All the peptides, altho ugh differing in biological activity, had almost identical secondary struct ures. Unlike alpha-fetoprotein, the three peptides have low amounts of alph a -helix. Trifluoroethanol has the ability to convert peptides into a helic al conformation when they have a propensity for that structure. At trifluor oethanol concentrations of 20% and higher, the alanine and glycine peptides were changed into highly helical structures.