癌症是人类致死的原因之一。高效特异的治癌药物设计与合成是学术界公认的科研热点和难点。近日，美国化学学会属下的知名杂志Journal of Chemical Information and Modeling以封面文章推出了高效特异性识别与抑制癌细胞的多肽分子新药物。这是研究生院化学与化工学院博士生崔巍同学与其导师计明娟教授等人通过计算机辅助设计完成的重要研究成果。
文章提出，G3BP是在很多肿瘤细胞中高表达的一种蛋白质分子，围绕该蛋白寻找特异性抗肿瘤药物是重要治疗手段之一。
他们应用分子动力学模拟方法，从理论上分析了涉及G3BP的蛋白质相互作用，并依据获取的Ras-GAP蛋白与G3BP蛋白质识别的重要信息设计合成了两条全新序列的抗肿瘤多肽分子。细胞实验表明，这两条多肽不仅可以增强肿瘤细胞对顺铂等传统抗肿瘤药物的敏感性，而且多肽本身对肿瘤细胞也有显著的抑制作用，其药理活性显著高于国际上其他研究人员此前已报道的多肽分子。更重要的是，该研究成果设计合成的抗肿瘤多肽药物分子对肿瘤细胞显示出很高的特异性，并对正常细胞的毒性远低于同剂量的顺铂药物。
该工作对进一步研发全新机理的特异靶向性抗肿瘤新药提供了理论和实验依据，具有重要的学术意义和应用价值。(生物谷Bioon.com)
生物谷推荐原文出处：
J. Chem. Inf. Model. DOI: 10.1021/ci900404p
Structure-Based Design of Peptides against G3BP with Cytotoxicity on Tumor Cells
Wei Cui?, Zhuo Wei?, Quan Chen?, Yuanhua Cheng, Lingling Geng§, Jian Zhang§, Jianhua Chen*§, Tingjun Hou*? and Mingjuan Ji*?
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.
