Exploring the Diversity of Cysteine-Rich Natural Product Peptides via MS/MS Fingerprint Ions.

Exploring the Diversity of Cysteine-Rich Natural Product Peptides via MS/MS Fingerprint Ions.
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DOI:
10.1021/jasms.0c00078
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发表时间:
2020-09-02
影响因子:
3.2
通讯作者:
Hicks LM
Hicks LM
中科院分区:
化学3区
文献类型:
--
作者:
Parsley NC;Williams OL;Hicks LM

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天然产物提取物存在固有的复杂基质,在这种基质中,新的生物活性肽种类的鉴定受到低丰度质量和显著的结构和序列多样性的挑战。此外,发现的努力往往导致对已知化合物的重新鉴定,而在体内或样品处理过程中产生的修饰可能会模糊真正的序列身份。在此,我们基于高序列同源性的区域,确定了环核苷酸(cyclotides)的质谱(MS2)“指纹”离子特征。环核苷酸是一种多样且具有生物活性的富含半胱氨酸的植物肽家族。我们将质移分析与MS2光谱指纹离子与CyBase (cyclotide数据库)交叉引用相结合,以识别堇菜中可能已经表征的质量种和常见修饰的质量种提取物中的独特质量种。该方法扩展到相关的一类富含半胱氨酸的肽,胰蛋白酶抑制剂,使用表征的植物物种Lagenaria siceraria。结合大量MS2离子的观察和质量位移分析,我们鉴定了一组新的小的,高度二硫结合的富含半胱氨酸的L. siceraria肽。我们鉴定了质谱(MS2)“指纹”离子特征的环核苷酸,一个多样化的和生物活性的家族植物半胱氨酸丰富的肽,基于高序列同源区域。质移分析与MS2光谱指纹离子相结合,以识别中提琴提取物中可能已经表征的和常见修饰的独特质种。
Natural product extracts present inherently complex matrices in which the identification of novel bioactive peptide species is challenged by low abundance masses and significant structural and sequence diversity. Additionally, discovery efforts often result in the re-identification of known compounds, where modifications derived in vivo or during sample handling may obscure true sequence identity. Herein, we identify mass spectral (MS2) “fingerprint” ions characteristic of cyclotides, a diverse and biologically active family of botanical cysteine-rich peptides, based on regions of high sequence homology. We couple mass shift analysis with MS2 spectral fingerprint ions cross referenced with CyBase - a cyclotide database - to discern unique mass species in Viola communis extracts from mass species that are likely already characterized and those with common modifications. The approach is extended to a related class of cysteine-rich peptide, the trypsin inhibitors, using the characterized botanical species Lagenaria siceraria. Coupling the observation of highly abundant MS2 ions with mass shift analysis, we identify a new set of small, highly disulfide bound cysteine-rich L. siceraria peptides. We identify mass spectral (MS2) “fingerprint” ions characteristic of cyclotides, a diverse and biologically active family of botanical cysteine-rich peptides, based on regions of high sequence homology. Mass shift analysis is coupled with MS2 spectral fingerprint ions to discern unique mass species in Viola extracts from mass species that are likely already characterized and those with common modifications.
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