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题名: Amphipathicity Determines Different Cytotoxic Mechanisms of Lysine- or Arginine-Rich Cationic Hydrophobic Peptides in Cancer Cells
作者: Liu, XL(刘晓丽); Cao, R; Wang, S(汪莎); Jia, JL(贾俊丽); Fei, H(费浩)
通讯作者: Fei, H(费浩)
刊名: JOURNAL OF MEDICINAL CHEMISTRY
发表日期: 2016
DOI: 10.1021/acs.jmedchem.5b02016
卷: 59, 期:11
收录类别: SCI ; EI
文章类型: 期刊论文
部门归属: 纳米生物医学与安全研究部
英文摘要: Cationic amphipathic peptides (CAPs) are known to be able to cause membrane destabilization and induce cell death, yet how the hydrophobicity, amphipathicity, and lysine (K)/arginine (R) composition synergistically affect the peptide activity remains incompletely understood. Here, we designed a panel of peptides based on the well-known anticancer peptide KLA. Increasing hydrophobicity enhanced the cytotoxicities of both the K- and R-rich peptides. Peptides with an intact amphipathic helical interface can cause instant cell death through a membrane lysis mechanism. Interestingly, rearranging the residue positions to minimize amphipathicity caused a great decrease of cytotoxicity to the K-rich peptides but not to the R-rich peptides. The amphipathicity-minimized R-rich peptide 6 (RL2) (RLLRLLRLRRLLRL-NH2) penetrated the cell membrane and induced caspase-3-dependent apoptotic cell death. We found that the modulation of hydrophobicity, amphipathicity, and K/R residues leads to distinct mechanisms of action of cationic hydrophobic peptides. Amphipathicity-reduced, arginine-rich cationic hydrophobic peptides (CHPs) may represent a new class of peptide therapeutics.
关键词[WOS]: ANTIMICROBIAL PEPTIDES ; PROAPOPTOTIC PEPTIDE ; LYTIC PEPTIDES ; IRIDIUM(III) COMPLEX ; AMPHIPHILIC PEPTIDES ; MEMBRANES ; STRESS ; APOPTOSIS ; TOXICITY ; PROTEINS
语种: 英语
JCR小类分区: 二区
WOS记录号: WOS:000377842500008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.sinano.ac.cn/handle/332007/4764
Appears in Collections:纳米生物医学与安全研究部_费浩团队_期刊论文

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Recommended Citation:
Liu, XL,Cao, R,Wang, S,et al. Amphipathicity Determines Different Cytotoxic Mechanisms of Lysine- or Arginine-Rich Cationic Hydrophobic Peptides in Cancer Cells[J]. JOURNAL OF MEDICINAL CHEMISTRY,2016,59(11).
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