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通过纳米孔鉴定和检测一种肽生物标志物及其对映体。

Identification and Detection of a Peptide Biomarker and Its Enantiomer by Nanopore.

作者信息

Ratinho Laura, Bacri Laurent, Thiebot Bénédicte, Cressiot Benjamin, Pelta Juan

机构信息

Université Paris-Saclay, Univ Evry, CY Cergy Paris Université, CNRS, LAMBE, 95000, Cergy, France.

Université Paris-Saclay, Univ Evry, CY Cergy Paris Université, CNRS, LAMBE, 91025, Evry-Courcouronnes, France.

出版信息

ACS Cent Sci. 2024 May 3;10(6):1167-1178. doi: 10.1021/acscentsci.4c00020. eCollection 2024 Jun 26.

Abstract

Until now, no fast, low-cost, and direct technique exists to identify and detect protein/peptide enantiomers, because their mass and charge are identical. They are essential since l- and d-protein enantiomers have different biological activities due to their unique conformations. Enantiomers have potential for diagnostic purposes for several diseases or normal bodily functions but have yet to be utilized. This work uses an aerolysin nanopore and electrical detection to identify vasopressin enantiomers, l-AVP and d-AVP, associated with different biological processes and pathologies. We show their identification according to their conformations, in either native or reducing conditions, using their specific electrical signature. To improve their identification, we used a principal component analysis approach to define the most relevant electrical parameters for their identification. Finally, we used the Monte Carlo prediction to assign each event type to a specific l- or d-AVP enantiomer.

摘要

到目前为止,还没有快速、低成本且直接的技术来识别和检测蛋白质/肽对映体,因为它们的质量和电荷相同。由于左旋和右旋蛋白质对映体因其独特的构象而具有不同的生物活性,所以它们至关重要。对映体在多种疾病或正常身体功能的诊断方面具有潜力,但尚未得到利用。这项工作使用气单胞菌溶素纳米孔和电学检测来识别与不同生物过程和病理相关的加压素对映体,即左旋精氨酸加压素(l-AVP)和右旋精氨酸加压素(d-AVP)。我们展示了在天然或还原条件下,根据它们的构象,利用其特定的电信号特征来识别它们。为了提高识别效果,我们使用主成分分析方法来确定用于识别它们的最相关电参数。最后,我们使用蒙特卡罗预测将每种事件类型分配给特定的左旋或右旋精氨酸加压素对映体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3026/11212137/fdd2a124ac42/oc4c00020_0001.jpg

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