A Novel Membrane-Permeable Breast-Targeting Pro-Apoptotic Peptide for Treatment of Breast Cancer
Abstract
In this project, the authors are trying to create a novel peptide with three properties: capable of membrane permeability, capable of targeting the breast, and capable of inducing apoptosis. The peptide is expected to be able to induce apoptosis specifically in breast cancer cells. It will be tested as a single therapeutic agent as well as in combination with chemotherapeutic drugs to treat breast cancer. In the first step of the project, the authors synthesized the breast-targeting, membrane permeable, pro-apoptotic peptide. The BH3 peptide of Bid (EDIIRNIARHLAQVGDSMDR) was synthesized with eight d-arginine residues at the N-terminus with a glycine linker residue, followed by a breast-homing sequence (CPGPEGAGC) at the C-terminal. A control peptide with a mutation in the BH3 domain also was synthesized: r8-BH3(L/E)-CPGPEGAGC. Next, they tested the therapeutic efficacy of the peptide in treating breast cancer. The peptide was first tested for apoptosis induction in vitro in cultured breast cancer MCF-7 cells. Unfortunately, the peptide failed to induce apoptosis in MCF-7 cells at the concentrations tested. The authors are in the process of producing an alternative peptide that has a similar design and predicted functions, but with a stronger apoptosis-inducing capability. The new peptide has a hydrocarbon-stapled BH3 helix. The new peptide will be tested for its apoptosis-inducing activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA447290
Entities
People
- Bin Guo
Organizations
- North Dakota State University