Myostatin inhibitory peptides in sports drug testing

IF 2.6 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Drug Testing and Analysis Pub Date : 2023-03-22 DOI:10.1002/dta.3473

Katja Walpurgis, Johannes Agricola, Andreas Thomas, Mario Thevis

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引用次数: 2

Abstract

Across species, skeletal muscle mass is negatively regulated by the TGF-β cytokine myostatin (MSTN). Inhibitors of this growth factor and its signaling pathways are therefore not only promising therapeutics for muscular diseases but also potential performance-enhancing agents in sports. Within this study, protein precipitation and liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) were employed to develop a detection method for six novel MSTN inhibitory peptides derived from the regulatory MSTN propeptide and the natural MSTN inhibitor follistatin (FST) from doping control serum samples. The approach was comprehensively characterized and found to allow for a specific detection down to concentrations of 3–9 ng/mL. Moreover, several potential metabolites of the drug candidates referred to as DF-3, DF-25, and Peptide 7 were identified as valuable complementary analytical targets for doping control analytical assays. Overall, the acquired data pave the way for an implementation of MSTN inhibitory peptides into routine sports drug testing. Even though no drug candidate has obtained clinical approval yet, a proactive development of detection assays is of utmost importance to deter athletes from misusing such compounds, which are readily available for research purposes and on the black market.

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运动药物检测中的肌肉生长抑制素抑制肽。

在所有物种中，骨骼肌质量受到TGF-β细胞因子肌生长抑制素(MSTN)的负调控。因此，这种生长因子及其信号通路的抑制剂不仅是治疗肌肉疾病的有希望的药物，而且是潜在的提高运动成绩的药物。在本研究中，采用蛋白沉淀和液相色谱-高分辨率串联质谱(LC-HRMS/MS)技术建立了一种检测兴奋剂对照血清样品中6种新型MSTN抑制肽的方法，这些抑制肽来源于MSTN调节前肽和天然MSTN抑制剂卵泡listatin (FST)。该方法被全面表征，并发现允许特定的检测浓度下降到3-9 ng/mL。此外，候选药物的几种潜在代谢物，如DF-3、DF-25和Peptide 7，被确定为兴奋剂控制分析分析的有价值的补充分析靶点。总的来说，获得的数据为MSTN抑制肽在常规运动药物测试中的实施铺平了道路。尽管目前还没有候选药物获得临床批准，但积极发展检测分析对于阻止运动员滥用这些化合物至关重要，因为这些化合物很容易用于研究目的和黑市。

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来源期刊

Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

5.90

自引率

24.10%

发文量

191

审稿时长

2.3 months

期刊介绍： As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.