Stearylated Antimicrobial Peptide Melittin and Its Retro Isomer for Efficient Gene Transfection

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• 作者：Wei Zhang ; Jingjing Song ; Ranran Liang ; Xin Zheng ; Jianbo Chen ; Guolin Li ; Bangzhi Zhang ; Xiang Yan ; Rui Wang
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：November 20, 2013
• 年：2013
• 卷：24
• 期：11
• 页码：1805-1812
• 全文大小：417K
• 年卷期：v.24,no.11(November 20, 2013)
• ISSN：1520-4812

文摘

A crucial bottleneck in nonviral vector-mediated gene delivery is poor endosomal escape. Here, we constructed novel gene vectors by coupling the stearyl moiety to the N-terminus of the antimicrobial peptide melittin (stearyl-Mel) and its retro isomer (stearyl-rMel) due to their high membrane-lytic activity. As expected, stearyl-Mel showed obvious increases in endosome-lytic activity and transfection efficiency compared with the reported stearyl-TP10. More gratifyingly, the transfection efficiency of stearyl-rMel was around 10-fold greater than that of stearyl-Mel and almost reached the transfection levels of Lipofectamine 2000 due to the enhanced endosome-lytic activity. Furthermore, the stearyl-rMel/p53 plasmid complex exhibited higher p53 expression and antitumor activity than stearyl-Mel, confirming the fact that stearyl-rMel displayed higher transfection efficiency. Taken together, the combination of the stearyl moiety with retro melittin provides a novel framework for the development of excellent nonviral gene vectors.