Impurity profiling quality control testing of synthetic peptides using liquid chromatography-photodiode array-fluorescence and liquid chromatography-electrospray ionization-mass spectrometry: The obestatin case

Impurity profiling quality control testing of synthetic peptides using liquid chromatography-photodiode array-fluorescence and liquid chromatography-electrospray ionization-mass spectrometry: The obestatin case
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DOI:
10.1016/j.ab.2008.02.014
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发表时间:
2008-05-15
影响因子:
2.9
通讯作者:
Burvenich, Christian
Burvenich, Christian
中科院分区:
生物学4区
文献类型:
--
作者:
De Spiegeleer, Bart;Vergote, Valentijn;Burvenich, Christian

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在发表了几篇相互矛盾的文章后,GPR39受体的发现者最近报道了无法重现GPR39受体在体外与Obestatin结合和激活的原始发现,并提出了几个合理的假设。基于其中一个假设(即存在杂质),对从五个不同制造商获得的不同研究小组使用的奥贝他汀肽进行了全面的肽鉴定和杂质谱分析。我们发现,其中一个被检查的产品实际上是完全不同的多肽,并且三分之二的其他多肽的质量不足以进行体外和体内实验(即,多肽纯度低于95%和/或单个杂质超过1%)。这些观察结果质疑文献中报道的关于奥贝他汀活性的不同结论。因此,我们强烈建议在将任何多肽用于生物医学研究之前进行适当的质量控制测试。(C)2008 Elsevier Inc.保留所有权利。
Following several conflicting publications, the inability to reproduce the original findings on in vitro obestatin binding and activation of GPR39 receptors was recently reported by its discoverers, and several hypotheses to rationalize these findings were proposed. Based on one of these postulations (i.e., presence of impurities), peptide identity and impurity profiles were thoroughly evaluated on obestatin peptides obtained from five different manufacturers, as used by the different research groups. We found that one of the products examined was in reality a totally different peptide and that the quality of two-thirds of the other peptides was insufficient for in vitro and in vivo experiments (i.e., peptide purity less than 95% and/or individual impurities exceeding 1%). These observations question the divergent conclusions reported in the literature about the activity of obestatin. Therefore, we strongly recommend appropriate quality control testing before using any peptides for biomedical research purposes. (C) 2008 Elsevier Inc. All rights reserved.