The effect of halogenation on the antimicrobial activity, antibiofilm activity, cytotoxicity and proteolytic stability of the antimicrobial peptide Jelleine-I
The effect of halogenation on the antimicrobial activity, antibiofilm activity, cytotoxicity and proteolytic stability of the antimicrobial peptide Jelleine-I
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DOI：
10.1016/j.peptides.2018.11.006
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发表时间：
2019-02-01
期刊：
影响因子：
3
通讯作者：
Wang, Kairong
中科院分区：
文献类型：
--
作者：
Jia, Fengjing;Zhang, Yi;Wang, Kairong
抗菌肽（AMP）被认为是一类很有前景的针对细菌和真菌的抗菌剂。为了促进AMPs的临床应用，应进一步提高其抗菌活性和对蛋白酶降解的敏感性。抗菌肽 Jelleine-I 最初是从蜜蜂 (Apis mellifera) 的蜂王浆中分离出来的，具有短序列 PFKLSLHL-NH2 (953.24 Da)。在此，设计并合成了一系列抗菌肽Jelleine-I的卤化衍生物。结果表明，卤化后其体外抗菌活性、抗生物膜活性和体内抗菌功效均提高1-8倍。此外，通过卤化，Jelleine-I 的蛋白水解稳定性提高了 10-100 倍。同时，卤化衍生物保留了可忽略不计的溶血活性和细胞毒性。其中，氯-Jelleine-I（Cl-J-I）、溴-Jelleine-I（Br-J-I）和碘-Jelleine-I（I-J-I）的抗菌活性和抗生物膜活性均优于氟-Jelleine-I（F-J-I）。 Br-J-I和I-J-I对酶和血清降解的稳定性优于F-J-I和Cl-J-I。总之，这项研究可能提供一种有用的策略，通过卤化来增强抗菌功效和蛋白水解稳定性。卤化衍生物Cl-J-I、Br-J-I和I-J-I可被认为是对抗微生物感染的潜在抗菌剂。
Antimicrobial peptides (AMPs) are believed to be a promising class of antimicrobial agents against bacteria and fungi. To promote the clinical use of AMPs, their antimicrobial activity and susceptibility to protease degradation should be further improved. The antimicrobial peptide Jelleine-I was originally isolated from the royal jelly of honeybees (Apis mellifera) with a short sequence of PFKLSLHL-NH2 (953.24 Da). Here, a series of halogenated derivatives of the antimicrobial peptide Jelleine-I were designed and synthesized. The results showed that the in vitro antimicrobial activity, antibiofilm activity and in vivo antimicrobial efficacy were enhanced 1-8-fold after halogenation. Additionally, the proteolytic stability of Jelleine-I was improved 10-100-fold by halogenation. Meanwhile, the halogenated derivatives retained negligible hemolytic activity and cytotoxicity. Among these derivatives, the antimicrobial activity and antibiofilm activity of chlorine-Jelleine-I (Cl-J-I), bromine-Jelleine-I (Br-J-I), and iodine-Jelleine-I (I-J-I) were better than those of fluorine-Jelleine-I (F-J-I). The stabilities of Br-J-I and I-J-I against the degradation of enzymes and the serum were better than those of F-J-I and Cl-J-I. In conclusion, this study may offer a useful strategy to enhance antimicrobial efficacy and proteolytic stability by halogenation. The halogenated derivatives Cl-J-I, Br-J-I and I-J-I may be considered as potential antimicrobial agents against microbial infection.