抗真菌脂肽 iturin A 类似物的全合成及其对 F. graminearum 的生物活性评估

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Periklis Karamanis, Jimmy Muldoon, Cormac D. Murphy, Marina Rubini
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引用次数: 0

摘要

抗真菌抗药性对人类健康和食品安全都构成了重大威胁,因此研究新型抗真菌剂势在必行。Iturin A 是由芽孢杆菌产生的一种环状脂肽,对多种病原体具有明显的抗真菌特性。它的合成难度很大,主要是由于其结构中存在的 β-氨基脂肪酸的合成非常费力,这阻碍了对其作用模式的研究和更强效类似物的开发。在这项研究中,我们简便地合成了含有烷基化半胱氨酸残基的具有生物活性的 iturin A 类似物。为了评估新引入氨基酸的立体化学结构对生物活性的影响,我们合成了两种烷基化半胱氨酸残基构型相反的类似物。对禾谷镰刀菌(F. graminearum)进行的抗真菌试验表明,新型类似物具有生物活性,可用作设计新类似物和进行结构-活性关系研究的合成模型。实验还突出了β-氨基酸在天然结构中的重要性以及氨基脂肪酸立体化学的作用,因为D构型的类似物比L构型的类似物具有更强的抗真菌性能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Total synthesis of antifungal lipopeptide iturin A analogues and evaluation of their bioactivity against F. graminearum

Total synthesis of antifungal lipopeptide iturin A analogues and evaluation of their bioactivity against F. graminearum

Total synthesis of antifungal lipopeptide iturin A analogues and evaluation of their bioactivity against F. graminearum

The pursuit of novel antifungal agents is imperative to tackle the threat of antifungal resistance, which poses major risks to both human health and to food security. Iturin A is a cyclic lipopeptide, produced by Bacillus sp., with pronounced antifungal properties against several pathogens. Its challenging synthesis, mainly due to the laborious synthesis of the β-amino fatty acid present in its structure, has hindered the study of its mode of action and the development of more potent analogues. In this work, a facile synthesis of bioactive iturin A analogues containing an alkylated cysteine residue is presented. Two analogues with opposite configurations of the alkylated cysteine residue were synthesized, to evaluate the role of the stereochemistry of the newly introduced amino acid on the bioactivity. Antifungal assays, conducted against F. graminearum, showed that the novel analogues are bioactive and can be used as a synthetic model for the design of new analogues and in structure–activity relationship studies. The assays also highlight the importance of the β-amino acid in the natural structure and the role of the stereochemistry of the amino fatty acid, as the analogue with the D configuration showed stronger antifungal properties than the one with the L configuration.

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来源期刊
Journal of Peptide Science
Journal of Peptide Science 生物-分析化学
CiteScore
3.40
自引率
4.80%
发文量
83
审稿时长
1.7 months
期刊介绍: The official Journal of the European Peptide Society EPS The Journal of Peptide Science is a cooperative venture of John Wiley & Sons, Ltd and the European Peptide Society, undertaken for the advancement of international peptide science by the publication of original research results and reviews. The Journal of Peptide Science publishes three types of articles: Research Articles, Rapid Communications and Reviews. The scope of the Journal embraces the whole range of peptide chemistry and biology: the isolation, characterisation, synthesis properties (chemical, physical, conformational, pharmacological, endocrine and immunological) and applications of natural peptides; studies of their analogues, including peptidomimetics; peptide antibiotics and other peptide-derived complex natural products; peptide and peptide-related drug design and development; peptide materials and nanomaterials science; combinatorial peptide research; the chemical synthesis of proteins; and methodological advances in all these areas. The spectrum of interests is well illustrated by the published proceedings of the regular international Symposia of the European, American, Japanese, Australian, Chinese and Indian Peptide Societies.
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