Design and Development of Peptides from the Anti-Angiogenic Pigment Epithelial-Derived Factor for the Therapy of Prostate Cancer
Abstract
To create PEDF based therapy for hormone-refractory CaP we have proposed to generate short synthetic peptides corresponding to the 34-mer anti-angiogenic epitope of PEDF. The 3D structure of the 34-mer peptide was analyzed using Protean software in terms of relative hydrophobicity charge distribution and antigenic index. Three synthetic peptides covering the 34-mer fragment were generated and tested for the ability to reproduce anti-angiogenic effect of PEDF. All peptides (14, 18 and 23-mer) inhibited FGF-induced endothelial cell migration. Dose-response curves were generated and the potency of the peptides compared to native PEDF and the 34-mer. Neither of the peptides showed signs of toxicity at the doses tested. Although all peptides showed anti-angiogenic activity in migration assay only 18 and 23-mer induced apoptosis in endothelial cells. 18-mer peptide also blocked neovascularization induced by FGF as demonstrated in corneal assay. This peptide will be further tested in vivo in mouse model for ability to inhibit prostate tumor growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2006
- Accession Number
- ADA462755
Entities
People
- Yelena Mirochnik
Organizations
- Northwestern University