Synthesis, antimicrobial activity and conformational analysis of the class IIa bacteriocin pediocin PA-1 and analogs thereof.

Synthesis, antimicrobial activity and conformational analysis of the class IIa bacteriocin pediocin PA-1 and analogs thereof.
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DOI:
10.1038/s41598-018-27225-3
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发表时间:
2018-06-13
期刊:
影响因子:
4.6
通讯作者:
Biron E
Biron E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bédard F;Hammami R;Zirah S;Rebuffat S;Fliss I;Biron E

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抗菌肽pediocin PA-1是一种IIa类细菌素,可抑制几种临床相关病原体,包括李斯特菌。在这里,我们报告的合成和表征的整个pediocin PA-1和其新的类似物,使用固相和溶液相的策略相结合,以克服由于不稳定和不希望的反应的困难。由此合成的片球菌素PA-1是单核细胞增生李斯特菌的有效抑制剂(MIC = 6.8 nM),类似于由乳酸片球菌天然产生的细菌素。特别令人感兴趣的是,缺乏两个二硫键的线性类似物表征pediocin PA-1是有效的。一种线性类似物也是另一种重要的食源性病原体产气荚膜梭菌的强抑制剂。这些结果进行了讨论,在光的构象信息来自圆二色谱,溶液NMR光谱和构效关系的研究。
The antimicrobial peptide pediocin PA-1 is a class IIa bacteriocin that inhibits several clinically relevant pathogens including Listeria spp. Here we report the synthesis and characterization of whole pediocin PA-1 and novel analogs thereof using a combination of solid- and solution-phase strategies to overcome difficulties due to instability and undesired reactions. Pediocin PA-1 thus synthesized was a potent inhibitor of Listeria monocytogenes (MIC = 6.8 nM), similar to the bacteriocin produced naturally by Pediococcus acidilactici. Of particular interest is that linear analogs lacking both of the disulfide bridges characterizing pediocin PA-1 were as potent. One linear analog was also a strong inhibitor of Clostridium perfringens, another important food-borne pathogen. These results are discussed in light of conformational information derived from circular dichroism, solution NMR spectroscopy and structure-activity relationship studies.
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