Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Department of Chemistry, High Point University, High Point, North Carolina 27268, United States.
J Nat Prod. 2024 Mar 22;87(3):544-553. doi: 10.1021/acs.jnatprod.3c00939. Epub 2024 Feb 17.
, known as Greater Celandine, is a latex-bearing plant that has been leveraged for its anticancer and antimicrobial properties. Herein, aerial tissue is mined for the presence of antimicrobial peptides. A highly abundant cysteine-rich peptide with a length of 25 amino acids, deemed CM-AMP1, is characterized through multiple mass spectrometric approaches. Electron-activated dissociation is leveraged to differentiate between isoleucine and leucine residues and complement conventional collision-induced dissociation to gain full sequence coverage of the full-length peptide. CM-AMP1 shares little sequence similarity with any proteins in publicly available databases, highlighting the novelty of its cysteine landscape and core motif. The presence of three disulfide bonds in the native peptide confers proteolytic stability, and antimicrobial activity is greatly decreased upon the alkylation of the cysteine residues. Synthetic variants of CM-AMP1 are used to confirm the activity of the full-length sequence and the core motif. To assess the biological impact, was grown in a sublethal concentration of CM-AMP1 and quantitative proteomics was used to identify proteins produced by the bacteria under stress, ultimately suggesting a membrane lytic antimicrobial mechanism of action. This study integrates multiple analytical methods for molecular and biological characterization of a unique antimicrobial peptide identified from
,被称为蒲公英,是一种含有乳胶的植物,具有抗癌和抗菌特性。在此,从空中组织中提取具有抗菌活性的肽。一种高度丰富的含 25 个氨基酸的富含半胱氨酸的肽,被称为 CM-AMP1,通过多种质谱方法进行了表征。电子激活解离用于区分异亮氨酸和亮氨酸残基,并补充常规的碰撞诱导解离,以获得全长肽的完整序列覆盖。CM-AMP1 与公共数据库中任何蛋白质的序列相似性都很小,突出了其半胱氨酸景观和核心基序的新颖性。天然肽中存在三个二硫键赋予其蛋白水解稳定性,并且当半胱氨酸残基烷基化时,抗菌活性大大降低。CM-AMP1 的合成变体用于确认全长序列和核心基序的活性。为了评估生物学影响,在蒲公英生长在亚致死浓度的 CM-AMP1 中,并使用定量蛋白质组学来鉴定在应激下细菌产生的蛋白质,最终表明其具有膜溶解抗菌作用机制。本研究综合了多种分析方法,用于对从蒲公英中鉴定出的独特抗菌肽进行分子和生物学表征。