Structure-Based Design of Peptides against G3BP with Cytotoxicity on Tumor Cells

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• 作者：Wei Cui ; Zhuo Wei ; Quan Chen ; Yuanhua Cheng ; Lingling Geng ; Jian Zhang ; Jianhua Chen ; Tingjun Hou ; Mingjuan Ji
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2010
• 出版时间：March 22, 2010
• 年：2010
• 卷：50
• 期：3
• 页码：380-387
• 全文大小：305K
• 年卷期：v.50,no.3(March 22, 2010)
• ISSN：1549-960X

文摘

Herein, we report a successful application of molecular modeling techniques to design two novel peptides with cytotoxicity on tumor cells. First, the interactions between the nuclear transport factor 2 (NTF2)-like domain of G3BP and the SH3 domain of RasGAP were studied by a well-designed protocol, which combines homology modeling, protein/protein docking, molecular dynamics simulations, molecular mechanics/generalized born surface area (MM/GBSA) free energy calculations, and MM/GBSA free energy decomposition analysis together. Then, based on the theoretical predictions, two novel peptides were designed and synthesized for biological assays, and they showed an obvious sensitizing effect on cis-platin. Furthermore, the deigned peptides had no significant effects on normal cells, while cis-platin did. Our results demonstrate that it is feasible to use the peptides to enhance the efficacy of clinical drugs and to kill cancer cells selectively. We believe that our work should be very useful for finding new therapies for cancers.