基于Tat (49-57)抗菌肽的设计、合成与性质研究
收稿日期: 2017-08-21
修回日期: 2017-10-23
网络出版日期: 2017-10-31
基金资助
国家自然科学基金（Nos.21572046，21172054）资助项目.
Design, Synthesis and Properties of the Antibacterial Peptides Based on Tat(49-57)
Received date: 2017-08-21
Revised date: 2017-10-23
Online published: 2017-10-31
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21572046, 21172054).
基于细胞穿膜肽Tat（49-57） N端二肽修饰设计了4条阳离子型抗菌肽Tat（YG）、Tat（YY）、Tat（FG）和Tat（FF），并通过Fmoc多肽固相合成法进行合成，反相高效液相色谱分离纯化，经1H NMR、ESI-MS和元素分析对其结构进行表征，采用噻唑蓝（MTT）法测定其抑菌活性，利用多种光谱法研究其与小牛胸腺DNA（ct-DNA）的相互作用.MTT实验结果表明，Tat（YY）、Tat（FF）、Tat（FF）和Tat（YY）、Tat（FF）分别对大肠杆菌、鼠伤寒沙门菌、枯草杆菌、金黄色葡萄球菌的抑制效率最高的，且抗菌肽的溶血性都很小，但对真菌的增长没有明显抑制作用.与DNA的结合实验结果表明：Tat（49-57）及其衍生肽与DNA相互作用的主要模式是沟槽模式，衍生肽与DNA的相互作用能力增强，具有进一步改善设计成为优异抗菌药物的价值.
吕名秀, 买文鹏, 卢奎, 段冰潮, 赵玉芬 . 基于Tat (49-57)抗菌肽的设计、合成与性质研究[J]. 有机化学, 2018 , 38(1) : 148 -155 . DOI: 10.6023/cjoc201708042
Four novel cationic antibacterial peptide analogs were modified at the N-terminus of the cell-penetrating peptide transacting activator of transcription TAT(49-57) by attaching dipeptides. Peptides were synthesized through standard Fmoc solid-phase peptide synthesis procedures, purified by reversed-phase high performance liquid chromatography (RP-HPLC), and characterized by 1H NMR, ESI-MS and elemental analysis. Tat(YY), Tat(FF), Tat(FF) and Tat(YY), Tat(FF) demonstrated better antibacterial activities against E. coli, S. typhimurium, B. subtilis and S. aureus with low hemolysis. respectively, but had no inhibitory effect on fungus growth. The Tat(49-57) analogs inhibited the bacteria more effectively than Tat(49-57). The interactions between peptides and calf thymus DNA (ct-DNA) were investigated with multi-spectroscopic techniques. The results showed that both peptides could interact with DNA via the groove binding mode. Compared to TAT(49-57), antibacterial peptide analogs combined with DNA much closer via binding constants, which has the value to become an excellent antibacterial agent with further improved and designed.
[1] Otter, J. A. Lancet. Infect Dis. 2010, 10, 519.
[2] Fischbach, M. A.; Walsh, C. T. Science. 2009, 325, 1089.
[3] da Silva, B. R.; de Freitas, V. A. A.; Nascimento-Neto, L. G.; Carneiro, V. A.; Arruda, F. V. S.; de Aguiar, A. S. W.; Teixeira, E. H. Peptides 2012, 36, 315.
[4] König, E.; Zhou, M.; Wang, L.; Chen, T.; Bininda-Emonds, O. R.; Shaw, C. Toxicon 2012, 60, 967.
[5] Li, L. R.; Shi, Y. H.; Cheserek, M. J.; Su, G. F.; Le, G. W. Appl. Microbiol. Biotechnol. 2013, 97, 1711.
[6] Lindgren, M.; Rosenthal-Aizman, K.; Saar, K.; Eiríksdóttir, E.; Jiang, Y.; Sassian, M.; Östlund, P.; Hällbrink, M.; Langel, Ü. Biochem. Pharmacol. 2006, 71, 416.
[7] Palm, C.; Netzereab, S.; Hällbrink, M. Peptides 2006, 27, 1710.
[8] Han, K.; Jeon, M. J.; Kim, S. H. Mol. Cells 2001, 12:267.
[9] Jin, L. H.; Bahn, J. H.; Eum, W. S. Free Radical. Biol. Med. 2001, 31, 1509.
[10] Green, D. R.; Reed, J. C. Science 1998, 281, 1309.
[11] Frankel, A. D.; Pabo, C. O. Cell 1988, 55, 1189.
[12] Kim, C.; Lee, Y.; Kim, J. S.; Jeong, J. H.; Park, T. G. Langmuir 2010, 26, 14965.
[13] Brooks, H.; Lebleu, B. Adv. Drug Delivery Rev. 2005, 57, 559.
[14] Fukuda, R.; Takenaka, S.; Takagi, M. J. Chem. Soc., Chem. Commun. 1990, 1028.
[15] Sahoo, B. K.; Ghosh, K. S.; Bera, R.; Dasgupta, S. Chem. Phys. 2008, 351, 163.
[16] Charak, S.; Jangir, D. K.; Tyagi, G.; Mehrotra, R. J. Mol. Struct. 2011, 1000, 150.
[17] Alagesan, M.; Bhuvanesh, N. S.; Dharmaraj, N. Dalton Trans. 2013, 42, 7210.
[18] Kashanian, S.; Khodaei, M. M.; Pakravan, P. DNA Cell Biol. 2010, 29, 639.
[19] Sarwar, T.; Rehman, S. U.; Husain, M. A.; Ishqi, H. M.; Tabish, M. Int. J. Biol. Macromol. 2015, 73, 9.
[20] Feroz, S. R.; Mohamad, S. B.; Bujang, N.; Malek, S. N.; Tayyab, S. J. Agric. Food Chem. 2012, 60, 5899.
[21] Cui, F.; Huo, R.; Hui, G.; Lv, X.; Jin, J.; Zhang, G.; Xing, W. J. Mol. Struct. 2011, 1001, 104.
[22] Zhang, G.; Wang, L.; Zhou, X.; Li, Y.; Gong, D. J. Agric. Food Chem. 2014, 62, 991.
[23] Yan, M.; Wei, G. Asian J. Chem. 2012, 24, 2061.
[24] Shi, J. H.; Chen, J.; Wang, J.; Zhu, Y. Y. Spectrochim. Acta A. 2015, 136, 443.
[25] Shao, Y.; Sheng, X.; Li, Y.; Jia, Z. L.; Zhang, J. J.; Liu, F.; Lu, G. Y. Bioconjugate Chem. 2008, 19, 1840.
[26] Mukherjee, A.; Mondal, S.; Singh, B. Int. J. Biol. Macromol. 2017, 101, 527.
[27] Patel, S.; Patel, P.; Undre, S. B.; Pandya, S. R.; Singh, M.; Bakshi, S. J. Mol. Liq. 2016, 213, 304.
[28] Zhao, D.; Ma, L.; Lu, K.; Wu, J.; He, J. Res. Chem. Intermed. 2015, 41, 8591.
[29] Srishailam, A.; Kumar, Y. P.; Gabra, N. M.; Reddy, P. V.; Deepika, N.; Veerababu, N.; Satyanarayana, S. J. Fluoresc. 2013, 23, 897.
[30] Hou, F.; Li, J.; Pan, P.; Xu, J.; Liu, L.; Liu, W.; Song, B.; Li, N.; Wan, J.; Gao, H. Int. J. Antimicrob. Agents 2011, 38, 510.
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