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Metallocomplex-Peptide Interactions Studied by Ultrahigh Resolution Mass Spectrometry.
Journal of the American Society for Mass Spectrometry ( IF 3.1 ) Pub Date : 2020-02-24 , DOI: 10.1021/jasms.9b00054
Cookson K C Chiu 1 , Yuko P Y Lam 1 , Christopher A Wootton 1 , Mark P Barrow 1 , Peter J Sadler 1 , Peter B O'Connor 1
Affiliation  

The OsII arene anticancer complex [(η6-bip)Os(en)Cl]+ (Os1-Cl; where bip = biphenyl and en = ethylenediamine) binds strongly to DNA1 and biomolecules. Here we investigate the interaction between Os1-Cl and the model protein, BSA, using ultrahigh resolution Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). The specific binding location of Os1 on BSA was investigated with the use of collisionally activated dissociation (CAD) and electron capture dissociation (ECD). CAD MS/MS was found to dissociate the osmium complex from the metallo-peptide complex readily producing unmodified fragments and losing location information. ECD MS/MS, however, successfully retains the osmium modification on the peptides upon fragmentation allowing localization of metallocomplex binding. This study reveals that lysine is a possible binding location for Os1-Cl, apart from the expected binding sites at methionine, histidine, and cysteine. Using a nano liquid chromatography (nLC)-FT-ICR ECD MS/MS study, multiple binding locations, including the N-terminus and C-terminus of digested peptides, glutamic acid, and lysine were also revealed. These results show the multitargeting binding ability of the organo-osmium compound and can be used as a standard workflow for more complex systems, e.g., metallocomplex-cell MS analysis, to evaluate their behavior toward commonly encountered biomolecules.

中文翻译:

通过超高分辨率质谱研究金属络合物-肽相互作用。

OsII芳烃抗癌复合物[(η6-bip)Os(en)Cl] +(Os1-Cl;其中bip =联苯,en =乙二胺)与DNA1和生物分子牢固结合。在这里,我们使用超高分辨率傅立叶变换离子回旋共振质谱(FT-ICR MS)研究Os1-Cl与模型蛋白BSA之间的相互作用。使用碰撞激活解离(CAD)和电子捕获解离(ECD)研究了Os1在BSA上的特异性结合位置。发现CAD MS / MS可将complex络合物与金属肽络合物解离,从而容易产生未修饰的片段并丢失位置信息。然而,ECD MS / MS在断裂时成功地在肽上保留了modification修饰,从而使金属配合物结合得以定位。这项研究表明,除了蛋氨酸,组氨酸和半胱氨酸的预期结合位点以外,赖氨酸是Os1-Cl的可能结合位点。使用纳米液相色谱(nLC)-FT-ICR ECD MS / MS研究,还显示了多个结合位置,包括消化的肽的N端和C端,谷氨酸和赖氨酸。这些结果显示了有机-化合物的多靶点结合能力,可以用作更复杂系统(例如金属复杂细胞MS分析)的标准工作流程,以评估其对常见生物分子的行为。还发现了谷氨酸和赖氨酸。这些结果显示了有机-化合物的多靶点结合能力,可以用作更复杂系统(例如金属复杂细胞MS分析)的标准工作流程,以评估其对常见生物分子的行为。还发现了谷氨酸和赖氨酸。这些结果显示了有机-化合物的多靶点结合能力,可以用作更复杂系统(例如金属复杂细胞MS分析)的标准工作流程,以评估其对常见生物分子的行为。
更新日期:2020-02-24
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