Studies on a growth-inhibitory peptide derived from alpha-fetoprotein and some analogs

L. E. Eisele, H. Soldwedel, R. MacColl, G. J. Mizejewski, F. B. Mesfin, J. A. Bennett, T. T. Andersen, H. I. Jacobson

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


A 34-amino acid synthetic peptide was derived from the third domain of human alpha-fetoprotein, and the peptide was shown to inhibit estrogen-stimulated growth. Under certain conditions, however, the peptide lost growth-inhibitory activity. A biophysical study of the peptide was undertaken with a goal of obtaining completely reliable preparations. The peptide was studied using gel-filtration column chromatography as a function of peptide concentration and age of solution, and was found to exhibit complex aggregation behaviors. During the early period (0-3 h) after dissolving lyophilized peptide into pH 7.4 buffer, solutions were composed mostly of trimers. At higher peptide concentrations (≥3.0 g/L), the trimers aggregated extensively to a large aggregate (minimum size ≈ 102 peptides). At 5.0-8.0 g/L, these large aggregates increased in size (up to ≈ 146 peptides) until trimers were largely exhausted from solution. During the later times (>3 h) after sample preparation, the trimeric oligomer of the peptide dissociated slowly to form dimers for samples at 0.10-3.0 g/L. After their build-up, a very small number of dimers associated to form hexamers. Disulfide bonds stabilized the dimers as indicated by the conversion of dimers to trimers upon the addition of a reducing agent, and the failure of dimers to form in the presence of reducing agent. Reducing agent did not affect trimer or large aggregate formation. Trimers were found to be active in an assay monitoring inhibition of estrogen-stimulated growth, whereas dimers and large aggregates were inactive. The two cysteines in the peptide were modified to either S-methylcysteine or S-(2-aminoethyl)cysteine, and both derivatives showed significant growth-inhibition activity. A serine analog in which both cysteines were replaced had very different aggregation behavior than the cysteine peptide and lacked its growth inhibitory ability. Peptide aggregation is critically important in establishing the ability of the peptide to inhibit growth and have anticancer activity, but the state of its two cysteines is of little influence.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalJournal of Peptide Research
Issue number1
StatePublished - 2001
Externally publishedYes


  • Alpha-fetoprotein
  • Alpha-fetoprotein peptides
  • Anticancer peptides
  • Breast cancer studies
  • Disulfide bonds
  • Estrogen-dependent mouse uterus growth
  • Neoepitopes
  • Peptide aggregation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology


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