Synthesis and biological evaluation of novel aliphatic acid-conjugated antimicrobial peptides as potential agents with anti-tumor, multidrug resistance-reversing activity and enhanced stability
Synthesis and biological evaluation of novel aliphatic acid-conjugated antimicrobial peptides as potential agents with anti-tumor, multidrug resistance-reversing activity and enhanced stability
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新型脂肪酸缀合抗菌肽的合成和生物学评价，作为具有抗肿瘤、逆转多药耐药活性和增强稳定性的潜在药物
DOI：
10.1007/s00726-017-2482-6
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发表时间：
2017-08
期刊：
影响因子：
3.5
通讯作者：
Ge Liang
中科院分区：
文献类型：
--
作者：
Zhang Bo;Gu Haitao;Shi Wei;Li Huilan;Ma Guanglan;Chen Xiaolian;Qian Hai;Lin Haiyan;Huang Wenlong;Ge Liang
与传统的抗肿瘤药物相比，抗菌肽作为一种新型的抗肿瘤药物，具有特异性高、避免多药耐药等突出优点。BP100是一种多功能膜活性多肽，具有较高的抗菌活性。以BP100为先导肽，通过固相合成法设计合成了一系列脂肪链共轭多肽。生物学评价表明，这些多肽具有比BP100更好的抗癌活性。进一步的研究发现，这些多肽可以破坏细胞膜，触发细胞色素C释放到细胞质中，最终导致细胞凋亡。同时，这些多肽对多药耐药细胞也表现出有效的抗肿瘤活性，并具有多药耐药逆转作用。此外，将脂肪酸偶联到这些多肽上可以提高它们在血浆中的稳定性。综上所述，脂肪酸修饰的多肽可能是一种很有前途的抗癌药物。
Compared with traditional anti-tumor drugs, antimicrobial peptides as novel anti-tumor agents have prominent advantages of higher specificity and circumvention of multi-drug resistance. BP100 is a multifunctional membrane-active peptide with high antimicrobial activity. Taking BP100 as a lead peptide, we designed and synthesized a series of aliphatic chain-conjugated peptides through solid-phase synthesis. Biological evaluation revealed that these peptides exhibited better anti-cancer activity than BP100. Further investigations revealed that these peptides could disrupt the cell membrane and trigger the cytochrome C release into cytoplasm, which ultimately resulted in apoptosis. Meanwhile, these peptides also exhibited effective anti-tumor activity against multidrug resistant cells and had multidrug resistance-reversing effect. Additionally, conjugation of aliphatic acid to those peptides could enhance their stability in plasma. In conclusion, aliphatic acid-modified peptides might be promising anti-tumor agents for cancer therapy.
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DOI：
10.1042/bj2940001
发表时间：
1993-08
期刊：
The Biochemical journal
影响因子：
--
作者：
A. Zachowski
通讯作者：
A. Zachowski
影响因子：
3
作者：
Jie Zhou;Xue Li;Xiao-yun Zhu;Jian Sun;Qianqian Qiu;Wen-long Huang;Hai Qian
通讯作者：
Jie Zhou;Xue Li;Xiao-yun Zhu;Jian Sun;Qianqian Qiu;Wen-long Huang;Hai Qian
影响因子：
3.4
作者：
deKroon, AIPM;Dolis, D;deKruijff, B
通讯作者：
deKruijff, B
DOI：
10.1007/s00249-011-0682-7
发表时间：
2011-04-01
影响因子：
2
作者：
Splith, Katrin;Neundorf, Ines
通讯作者：
Neundorf, Ines
DOI：
10.1677/joe.0.1590093
发表时间：
1998-10
期刊：
The Journal of endocrinology
影响因子：
--
作者：
U. Ritzel;U. Leonhardt;M. Ottleben;A. Rühmann;K. Eckart;J. Spiess;G. Ramadori
通讯作者：
U. Ritzel;U. Leonhardt;M. Ottleben;A. Rühmann;K. Eckart;J. Spiess;G. Ramadori