AFP-Derived Peptides Which Stop Breast Cancer Growth
Abstract
Alpha-fetoprotein (AFP) is a glycoprotein produced during pregnancy by fetal yolk sac and by fetal liver and is a major protein constituent of fetal plasma throughout gestation. It has been shown that fetal physiological levels of human AFP inhibit estrogen-stimulated growth of human breast cancer. The purpose of our work is to derive a stable anti-breast cancer agent from AFP. In the past, we have identified a 14-mer peptide from the Domain III of AFP that retained the full antiestrotrophic activity AFP. In the past year, we have found that an octapeptide, P472-2 (EMTPVNPG) derived from the 14-mer peptide is the minimal sequence required to generate the antiestrotrophic activity of full-length AFP. Peptide P472-2 exhibited dose-dependent inhibition of growth of estrogen-stimulated immature mouse uterus with the optimal dose of 1 ug. P472-2 also inhibited tamoxifen-stimulated growth of immature mouse uterus. However, this activity of P472-2 was diminished during storage in the lyophilized state. Mass spectrometry analysis suggested that there were no chemical modifications during storage. Gel-filtration chromatography suggests that the peptide aggregates to form inactive species during storage. These results suggest that further chemical modification is required to generate an optimal analog with longer shelf-life.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385512
Entities
People
- Fassil Mesfin
- James A. Bennett
- Thomas T. Anderson
Organizations
- Albany Medical College