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Novel anoplin‐based (lipo)‐peptide models show potent antimicrobial activity
Journal of Peptide Science ( IF 1.8 ) Pub Date : 2021-01-27 , DOI: 10.1002/psc.3303 Vasileios Stergiou 1 , Dimitrios Krikorian 1 , Anna-Irini Koukkou 1 , Maria Sakarellos-Daitsiotis 1 , Eugenia Panou-Pomonis 1
Journal of Peptide Science ( IF 1.8 ) Pub Date : 2021-01-27 , DOI: 10.1002/psc.3303 Vasileios Stergiou 1 , Dimitrios Krikorian 1 , Anna-Irini Koukkou 1 , Maria Sakarellos-Daitsiotis 1 , Eugenia Panou-Pomonis 1
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The subject of this study is the synthesis and biological evaluation of anoplin‐based (Gly‐Leu‐Leu3‐Lys‐Arg5‐Ile‐Lys‐Thr8‐Leu‐Leu‐NH2)—designed (lipo)‐peptides, aiming at the development of new antibiotic substances. The design of synthetic compounds based on natural bioactive molecules is an optimistic strategy for the development of new pharmaceutics. Antimicrobial peptides (AMPs) and (lipo)‐peptides are two classes of promising compounds, with characteristics that allow them to express their activity by differentiated mechanisms of action. On this basis, anoplin, a natural AMP, was used as a scaffold to design five peptides and seven lipopeptide analogs of them. Substitutions were made on residues Leu3 and Arg5 of the interphase and on Thr8 of the polar phase, as well as N‐terminus conjunctions with octanoic and decanoic acid. The outcome of the biological evaluation revealed that some analogs might have substantial clinical potential. Specifically, Ano 1‐F, Ano 3‐F, Ano 4‐C10, and Ano 5‐F are strongly active against Gram‐negative bacteria at minimum inhibitory concentration (MIC) values of 3 μg/ml, while Ano 4‐F is active against Gram‐positive bacteria at 1 μg/ml. Ano 2‐C10, C10‐Gly‐Leu‐Lys3‐Lys‐Ile5‐Ile‐Lys‐Lys8‐Leu‐Leu‐NH2, is the most promising compound (MIC = 0.5 μg/ml) for the development of new pharmaceutics. The conformational features of the synthetic peptides were investigated by circular dichroism spectroscopy, and their physicochemical parameters were calculated. Our study shows that appropriate substitutions in the anoplin sequence in combination with Nα‐acylation may lead to new effective AMPs.
中文翻译：
新型anoplin（脂质）-肽模型显示出有效的抗菌活性
本研究的主题是基于 anoplin（Gly-Leu-Leu 3 -Lys-Arg 5 -Ile-Lys-Thr 8 -Leu-Leu-NH 2）设计的（脂质）肽的合成和生物学评价，旨在开发新的抗生素物质。基于天然生物活性分子的合成化合物的设计是开发新药的乐观策略。抗菌肽 (AMP) 和 (脂质) 肽是两类有前景的化合物，它们的特性使它们能够通过不同的作用机制表达其活性。在此基础上，使用天然 AMP 的 anoplin 作为支架设计了它们的 5 种肽和 7 种脂肽类似物。对残基 Leu 3进行替换和中间相的Arg 5和极性相的Thr 8上，以及与辛酸和癸酸的 N 端连接。生物学评估的结果表明，一些类似物可能具有巨大的临床潜力。具体而言，Ano 1-F、Ano 3-F、Ano 4-C 10和 Ano 5-F 在最低抑菌浓度 (MIC) 值为 3 μg/ml 时对革兰氏阴性菌具有很强的活性，而 Ano 4-F对革兰氏阳性菌有活性，浓度为 1 μg/ml。Ano 2-C 10 , C 10 -Gly-Leu-Lys 3 -Lys-Ile 5 -Ile-Lys-Lys 8 -Leu-Leu-NH 2, 是最有希望开发新药的化合物 (MIC = 0.5 μg/ml)。通过圆二色光谱研究合成肽的构象特征，并计算其理化参数。我们的研究表明，anoplin 序列中的适当取代与 N α酰化相结合可能会产生新的有效 AMP。
更新日期：2021-03-03
中文翻译：
新型anoplin（脂质）-肽模型显示出有效的抗菌活性
本研究的主题是基于 anoplin（Gly-Leu-Leu 3 -Lys-Arg 5 -Ile-Lys-Thr 8 -Leu-Leu-NH 2）设计的（脂质）肽的合成和生物学评价，旨在开发新的抗生素物质。基于天然生物活性分子的合成化合物的设计是开发新药的乐观策略。抗菌肽 (AMP) 和 (脂质) 肽是两类有前景的化合物，它们的特性使它们能够通过不同的作用机制表达其活性。在此基础上，使用天然 AMP 的 anoplin 作为支架设计了它们的 5 种肽和 7 种脂肽类似物。对残基 Leu 3进行替换和中间相的Arg 5和极性相的Thr 8上，以及与辛酸和癸酸的 N 端连接。生物学评估的结果表明，一些类似物可能具有巨大的临床潜力。具体而言，Ano 1-F、Ano 3-F、Ano 4-C 10和 Ano 5-F 在最低抑菌浓度 (MIC) 值为 3 μg/ml 时对革兰氏阴性菌具有很强的活性，而 Ano 4-F对革兰氏阳性菌有活性，浓度为 1 μg/ml。Ano 2-C 10 , C 10 -Gly-Leu-Lys 3 -Lys-Ile 5 -Ile-Lys-Lys 8 -Leu-Leu-NH 2, 是最有希望开发新药的化合物 (MIC = 0.5 μg/ml)。通过圆二色光谱研究合成肽的构象特征，并计算其理化参数。我们的研究表明，anoplin 序列中的适当取代与 N α酰化相结合可能会产生新的有效 AMP。
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