Optimizing anti-cancer peptides for use as novel cancer therapies

Anticancer peptides (ACPs) are small peptides (short chains of amino acids) that kill cancer cells by puncturing them or by triggering programmed cell suicide. In the lab, certain ACPs kill slow-growing and multidrug-resistant cancer cells, enhance action of anticancer drugs, and trigger the immune system to attack tumours. However, many also kill normal cells.

The goal of this work is to understand how the amino acid sequence contributes to selective cancer cell killing. This project will:

1. Screen large numbers of ACPs to identify amino acids that maximize cancer cell selectivity
2. Explore mechanisms of anti-tumour activity of our lead peptide Mastoparan

Peptide arrays allow hundreds of ACPs to be tested inexpensively. We will create many variant forms of the highly active ACP Mastoparan by substituting every amino acid in its chain with every other naturally occurring amino acid. A peptide array will be used to test which amino acids are vital for cancer cell killing and which ones harm normal cells.

Computer analysis will generate new ACP sequences with better predicted selectivity for cancer cells. The ACPs predicted to be most selective for cancer cells will be synthesized and screened, and the most promising ones will be tested for toxicity against human cancer cells and normal cells.

In addition, the immune system component of the anti-tumour activity of Mastoparan L will be explored further in vivo.

Ultimately, this project could give rise to peptides that selectively target cancer cells and induce an anti-tumour immune response.