Güell Imma, Vilà Sílvia, Badosa Esther, Montesinos Emilio, Feliu Lidia, Planas Marta
LIPPSO, Department of Chemistry, University of Girona, Campus Montilivi, 17003, Girona, Spain.
Laboratory of Plant Pathology, Institute of Food and Agricultural Technology-CIDSAV-XaRTA, University of Girona, Campus Montilivi, 17003, Girona, Spain.
Biopolymers. 2017 May;108(3). doi: 10.1002/bip.23012.
The search for novel antimicrobial agents to be used for plant protection has prompted us to design analogues incorporating non-natural amino acids. Herein, we designed and synthesized cyclic peptidotriazoles derived from the lead antimicrobial cyclic peptide c(Lys-Lys-Leu -Lys-Lys -Phe-Lys-Lys-Leu-Gln) (BPC194). In particular, Leu and Lys were replaced by a triazolyl alanine, a triazolyl norleucine or a triazolyl lysine. These peptides were screened for their antibacterial activity against Xanthomonas axonopodis pv. vesicatoria, Erwinia amylovora, and Pseudomonas syringae pv. syringae, for their hemolysis and for their phytotoxicity. Results showed that the type of triazolyl amino acid and the substituent present at the triazole influenced the antibacterial and hemolytic activities. Moreover, the position of this residue was also crucial for the hemolysis. The lead compounds BPC548 and BPC550 exhibited high antibacterial activity (MIC of 3.1 to 25 μM), low hemolysis (19 and 26% at 375 μM, respectively) and low phytotoxicity. Therefore, these analogues could be used as new leads for the development of effective agents to control pathogenic bacteria responsible for plant diseases of economic importance.
寻找用于植物保护的新型抗菌剂促使我们设计包含非天然氨基酸的类似物。在此，我们设计并合成了源自先导抗菌环肽c（Lys-Lys-Leu-Lys-Lys-Phe-Lys-Lys-Leu-Gln）（BPC194）的环肽三唑。特别地，亮氨酸和赖氨酸被三唑基丙氨酸、三唑基正亮氨酸或三唑基赖氨酸取代。对这些肽进行了针对番茄疮痂病菌、梨火疫病菌和丁香假单胞菌丁香致病变种的抗菌活性、溶血活性和植物毒性筛选。结果表明，三唑基氨基酸的类型和三唑上存在的取代基影响抗菌和溶血活性。此外，该残基的位置对溶血也至关重要。先导化合物BPC548和BPC550表现出高抗菌活性（MIC为3.1至25μM）、低溶血（在375μM时分别为19%和26%）和低植物毒性。因此，这些类似物可作为开发有效药剂以控制对具有经济重要性的植物病害负责的病原菌的新先导物。
