Synthesis of anticancer heptapeptides containing a unique lipophilic β2,2-amino acid building block

• Published in: Journal of peptide science 2012-03, Vol.18 (3), p.170-176
• Main Authors: Tørfoss, Veronika, Ausbacher, Dominik, Cavalcanti-Jacobsen, Cristiane de A., Hansen, Terkel, Brandsdal, Bjørn-Olav, Havelkova, Martina, Strøm, Morten B.
• Format: Article
• Language: eng ; jpn
• Subjects: 2-amino acids; anticancer peptides; heptapeptides; peptide synthesis; β2,2‐amino acids
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.1434

We report a series of synthetic anticancer heptapeptides (H‐KKWβ2,2WKK‐NH2) containing eight different central lipophilic β2,2‐amino acid building blocks, which have demonstrated high efficiency when used as scaffolds in small cationic antimicrobial peptides and peptidomimetics. The most potent peptides in the present study had IC50 values of 9–23 µm against human Burkitt's lymphoma and murine B‐cell lymphoma and were all nonhaemolytic (EC50 > 200 µm). The most promising peptide 10e also demonstrated low toxicity against human embryonic lung fibroblast cells and peripheral blood mononuclear cells and exceptional proteolytic stability. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd. We report a series of synthetic anticancer heptapeptides (H‐KKWβ2,2WKK‐NH2) containing a unique central lipophilic β2,2‐amino acid building block. The most potent peptides had IC50 values of 8–23 µm against human Burkitt's lymphoma and murine B‐cell lymphoma and were all nonhaemolytic (EC50 > 200 µm). A potent lead peptide 10e was developed that also demonstrated low toxicity against human embryonic lung fibroblast cells and peripheral blood mononuclear cells and exceptional proteolytic stability.