Synthesis of anticancer heptapeptides containing a unique lipophilic ß(2,2) -amino acid building block.

ABSTRACT

We report a series of synthetic anticancer heptapeptides (H-KKWß(2,2) WKK-NH(2)) containing eight different central lipophilic ß(2,2) -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 IC(50) values of 9-23 µm against human Burkitt's lymphoma and murine B-cell lymphoma and were all nonhaemolytic (EC(50) > 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.