Multiple functions of short synthetic enantiomeric peptides based on beetle defensins.

Four enantiomeric 9-mer peptides, D-peptides A (RLYLRIGRR-NH2), B (RLRLRIGRR-NH2), C (ALYLAIRRR-NH2), and D (RLLLRIGRR-NH2), were designed and synthesized on the basis of a beetle defensin antimicrobial peptide. These D-9-mer peptides have been reported to exhibit multiple functions, including antimicrobial and antiprotozoan activity, without cytotoxicity on normal fibroblasts and leukocyte cells. In this study, we found that the D-9-mer peptides inhibited telomerase activity (IC100 = 40 μM). A new peptide, D-peptide C2 (ALYLAIRRRRRRRR-NH2), designed from D-peptide C to translocate into the cytoplasm by a penetrating sequence (octa-arginine), showed extremely strong telomerase inhibitory activity (IC100 = 0.1 μM). D-Peptide C2 exhibited a great increase in cytotoxicity against various cancer cell lines (IC50 = 3.4–26.4 μM). However, the immediate death of the cells suggested that the high cytotoxicity was not an effect of telomerase inhibitory activity. Mitochondrial swelling assay and microscopical obser...