Multiple Functions of Short Synthetic Enantiomeric Peptides Based on Beetle Defensins
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概要
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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 observations of mitochondria indicated that the major target of the D-peptide C2 was the mitochondrial membrane.
著者
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Ishibashi Jun
Innate Immunity Res. Unit National Inst. Of The Agrobiological Sciences
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Ishibashi Jun
Department Of Agricultural Chemistry Faculty Of Agriculture The University Of Tokyo
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Iwasaki Takashi
Graduate School Of Life And Environmental Sciences Univ. Of Tsukuba
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TAYLOR DeMar
Institute of Agriculture and Forestry, University of Tsukuba
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YAMAKAWA Minoru
Graduate School of Life and Environmental Science, University of Tsukuba
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KUBO Masanori
Diagnostic Section, National Institute of Animal Health
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